10.1007/s40097-022-00472-7

Exploring nano-enabled CRISPR-Cas-powered strategies for efficient diagnostics and treatment of infectious diseases

  • Ankit Kumar Dubey1,
  • Vijai Kumar Gupta2,
  • Małgorzata Kujawska3,
  • Gorka Orive4,
  • Nam-Young Kim5,
  • Chen-zhong Li6,
  • Yogendra Kumar Mishra7,
  • Ajeet Kaushik*8,
  1. Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, 600036, Chennai, Tamil Nadu, IN
  2. Biorefining and Advanced Materials Research Center, Scotland’s Rural College (SRUC), Edinburgh, EH9 3JG, GB
  3. Department of Toxicology, Poznan University of Medical Sciences, Poznań, 60-631, PL
  4. NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, ES CIBER Bioengineering, Biomaterials and Nanomedicine (CIBERBBN), Institute of Health Carlos III, Madrid, ES Bioaraba Health Research Institute, Nanobiocel Research Group, Vitoria-Gasteiz, ES University Institute for Regenerative Medicine and Oral Implantology, UIRMI (UPV/EHU-Fundación Eduardo Anitua), Vitoria-Gasteiz, ES Singapore Eye Research Institute, Singapore, SG
  5. Department of Electronics Engineering, RFIC Bio Centre, NDAC Centre, RFIC Bio Centre, NDAC Centre, Kwangwoon University, Seoul, 01897, KR
  6. Center for Cellular and Molecular Diagnostics, Tulane University School of Medicine, New Orleans, LA, 70112, US Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA, 70112, US
  7. Mads Clausen Institute, NanoSYD, University of Southern Denmark, Sønderborg, 6400, DK
  8. NanoBioTech Laboratory, Health System Engineering, Department of Natural Sciences, Florida Polytechnic University, Lakeland, FL-33805, US

Published in Issue 14-02-2022

How to Cite

Dubey, A. K., Kumar Gupta, V., Kujawska, M., Orive, G., Kim, N.-Y., Li, C.- zhong, Kumar Mishra, Y., & Kaushik, A. (2022). Exploring nano-enabled CRISPR-Cas-powered strategies for efficient diagnostics and treatment of infectious diseases. Journal of Nanostructure in Chemistry, 12(5 (October 2022). https://doi.org/10.1007/s40097-022-00472-7
Crossref
Scopus
Google Scholar
Europe PMC

Abstract

Abstract Biomedical researchers have subsequently been inspired the development of new approaches for precisely changing an organism’s genomic DNA in order to investigate customized diagnostics and therapeutics utilizing genetic engineering techniques. Clustered Regulatory Interspaced Short Palindromic Repeats (CRISPR) is one such technique that has emerged as a safe, targeted, and effective pharmaceutical treatment against a wide range of disease-causing organisms, including bacteria, fungi, parasites, and viruses, as well as genetic abnormalities. The recent discovery of very flexible engineered nucleic acid binding proteins has changed the scientific area of genome editing in a revolutionary way. Since current genetic engineering technique relies on viral vectors, issues about immunogenicity, insertional oncogenesis, retention, and targeted delivery remain unanswered. The use of nanotechnology has the potential to improve the safety and efficacy of CRISPR/Cas9 component distribution by employing tailored polymeric nanoparticles. The combination of two (CRISPR/Cas9 and nanotechnology) offers the potential to open new therapeutic paths. Considering the benefits, demand, and constraints, the goal of this research is to acquire more about the biology of CRISPR technology, as well as aspects of selective and effective diagnostics and therapies for infectious illnesses and other metabolic disorders. This review advocated combining nanomedicine (nanomedicine) with a CRISPR/Cas enabled sensing system to perform early-stage diagnostics and selective therapy of specific infectious disorders. Such a Nano-CRISPR-powered nanomedicine and sensing system would allow for successful infectious illness control, even on a personal level. This comprehensive study also discusses the current obstacles and potential of the predicted technology. Graphical abstract

Keywords

  • Gene editing,
  • CRISPR/Cas,
  • Infectious diseases,
  • Nanomedicine,
  • Biosensor,
  • Diseases management,
  • Personalized healthcare

References

  1. Fauci (2001) Infectious diseases: considerations for the 21st Century (pp. 675-685) https://doi.org/10.1086/319235
  2. Menon et al. (2019) National burden estimates of Healthy Life Lost in India, 2017: an analysis using direct mortality data and indirect disability data (pp. E1675-E1684) https://doi.org/10.1016/S2214-109X(19)30451-6
  3. Morens et al. (2004) The challenge of emerging and re-emerging infectious diseases (pp. 242-249) https://doi.org/10.1038/nature02759
  4. Bakhrebah et al. (2018) CRISPR technology: new paradigm to target the infectious disease pathogens (pp. 3448-3452)
  5. Caliendo et al. (2013) Better tests, Better Care: Improved diagnostics for infectious diseases (pp. S139-170) https://doi.org/10.1093/cid/cit578
  6. Walker DH. Principles of diagnosis of infectious diseases. Pathobiol. Hum. Dis. 222–225 (2014)
  7. Watzinger et al. (2006) Detection and monitoring of virus infections by real-time PCR (pp. 254-298) https://doi.org/10.1016/j.mam.2005.12.001
  8. Foss et al. (2019) Clinical applications of CRISPR-based genome editing and diagnostics (pp. 1389-1399) https://doi.org/10.1111/trf.15126
  9. Verma et al. (2019) A CRISPR/Cas9 based polymeric nanoparticles to treat/inhibit microbial infections (pp. 44-52) https://doi.org/10.1016/j.semcdb.2019.04.007
  10. Rocha et al. (2020) Gene editing for treatment and prevention of human diseases: a global survey of gene editing-related researchers (pp. 852-862) https://doi.org/10.1089/hum.2020.136
  11. Torres-Ruiz and Rodriguez-Perales (2017) CRISPR/Cas9 technology: applications and human disease modelling (pp. 4-12) https://doi.org/10.1093/bfgp/elw025
  12. Trevisan et al. (2017) Genome editing technologies to fight infectious diseases (pp. 1001-1013) https://doi.org/10.1080/14787210.2017.1400379
  13. Strich and Chertow (2019) CRISPR/Cas biology and its application to infectious diseases (pp. 1307-1318) https://doi.org/10.1128/JCM.01307-18
  14. Mustafa and Makhawi (2021) SHERLOCK and DETECTR: CRISPR/Cas systems as potential rapid diagnostic tools for emerging infectious diseases (pp. e00745-e820) https://doi.org/10.1128/JCM.00745-20
  15. Yadav et al. (2021) CRISPR: A new paradigm of theranostics https://doi.org/10.1016/j.nano.2020.102350
  16. Yetisgin et al. (2020) Therapeutic nanoparticles and their targeted delivery applications https://doi.org/10.3390/molecules25092193
  17. Hillaireau and Couvreur (2009) Nanocarriers’ entry into the cell: relevance to drug delivery (pp. 2873-2896) https://doi.org/10.1007/s00018-009-0053-z
  18. Kumar et al. (2020) CRISPR/Cas system: an approach with potentials for COVID-19 diagnosis and therapeutics https://doi.org/10.3389/fcimb.2020.576875
  19. Kim et al. (2015) Digenome-seq: genome-wide profiling of CRISPR/Cas9 off-target effects in human cells (pp. 237-243) https://doi.org/10.1038/nmeth.3284
  20. Lone et al. (2018) CRISPR/Cas9 system: a bacterial tailor for genomic engineering
  21. Rodríguez-Rodríguez et al. (2019) Genome editing: a perspective on the application of CRISPR/Cas9 to study human diseases (Review) (pp. 1559-1574)
  22. Jiang and Doudna (2017) CRISPR/Cas9 structures and mechanisms (pp. 505-529) https://doi.org/10.1146/annurev-biophys-062215-010822
  23. Kennedy and Cullen (2017) Gene Editing: a new tool for viral disease (pp. 401-411) https://doi.org/10.1146/annurev-med-051215-031129
  24. Barrangou et al. (2007) CRISPR provides acquired resistance against viruses in prokaryotes (pp. 1709-1712) https://doi.org/10.1126/science.1138140
  25. Nishimasu et al. (2014) Crystal structure of Cas9 in complex with guide RNA and target DNA (pp. 935-949) https://doi.org/10.1016/j.cell.2014.02.001
  26. Jolany Vangah et al. (2020) CRISPR-based diagnosis of infectious and noninfectious diseases https://doi.org/10.1186/s12575-020-00135-3
  27. Hille and Charpentier (2016) CRISPR/Cas: biology, mechanisms and relevance https://doi.org/10.1098/rstb.2015.0496
  28. Ribeiro et al. (2018) Protein engineering strategies to expand CRISPR/Cas9 applications https://doi.org/10.1155/2018/1652567
  29. Xu et al. (2019) Delivery of CRISPR/Cas9 for therapeutic genome editing https://doi.org/10.1002/jgm.3107
  30. Zhu and Huang (2018) Recent advances in structural studies of the CRISPR/Cas-mediated genome editing tools (pp. 438-451) https://doi.org/10.1093/nsr/nwy150
  31. Koonin et al. (2017) Diversity, classification and evolution of CRISPR/Cas systems (pp. 67-78) https://doi.org/10.1016/j.mib.2017.05.008
  32. Pinilla-Redondo et al. (2020) Type IV CRISPR/Cas systems are highly diverse and involved in competition between plasmids (pp. 2000-2012) https://doi.org/10.1093/nar/gkz1197
  33. Makarova and Koonin (2015) Annotation and Classification of CRISPR/Cas Systems (pp. 47-75) https://doi.org/10.1007/978-1-4939-2687-9_4
  34. Mohanraju et al. (2016) Diverse evolutionary roots and mechanistic variations of the CRISPR/Cas systems https://doi.org/10.1126/science.aad5147
  35. Moon SB, Kim DY, Ko JH, Kim YS. Recent advances in the CRISPR genome editing tool set. Exp. Mo.l Med.
  36. 51
  37. .1–11 (2019).
  38. Hsu et al. (2014) Development and applications of CRISPR/Cas9 for genome engineering (pp. 1262-1278) https://doi.org/10.1016/j.cell.2014.05.010
  39. Liu et al. (2020) Application of different types of CRISPR/Cas-based systems in bacteria https://doi.org/10.1186/s12934-020-01431-z
  40. O'Connell (2019) Molecular Mechanisms of RNA Targeting by Cas13-containing Type VI CRISPR/Cas Systems (pp. 66-87) https://doi.org/10.1016/j.jmb.2018.06.029
  41. Toro et al. (2019) Recruitment of Reverse Transcriptase-Cas1 Fusion Proteins by Type VI-A CRISPR/Cas Systems https://doi.org/10.3389/fmicb.2019.02160
  42. Gasiunas et al. (2012) Cas9-crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria (pp. E2579-E2586) https://doi.org/10.1073/pnas.1208507109
  43. Rath et al. (2015) The CRISPR/Cas immune system: biology, mechanisms and applications (pp. 119-128) https://doi.org/10.1016/j.biochi.2015.03.025
  44. Carte et al. (2008) Cas6 is an endoribonuclease that generates guide RNAs for invader defense in prokaryotes (pp. 3489-3496) https://doi.org/10.1101/gad.1742908
  45. Pougach et al. (2010) Transcription, processing and function of CRISPR cassettes in Escherichia coli (pp. 1367-1379) https://doi.org/10.1111/j.1365-2958.2010.07265.x
  46. Charpentier et al. (2015) Biogenesis pathways of RNA guides in archaeal and bacterial CRISPR/Cas adaptive immunity (pp. 428-441) https://doi.org/10.1093/femsre/fuv023
  47. Carte et al. (2014) The three major types of CRISPR/Cas systems function independently in CRISPR RNA biogenesis in Streptococcus thermophilus 93(1) (pp. 98-112) https://doi.org/10.1111/mmi.12644
  48. Nam et al. (2012) Cas5d protein processes pre-crRNA and assembles into a cascade-like interference complex in subtype I-C/Dvulg CRISPR/Cas system (pp. 1574-1584) https://doi.org/10.1016/j.str.2012.06.016
  49. Gasiunas et al. (2014) Molecular mechanisms of CRISPR-mediated microbial immunity (pp. 449-465) https://doi.org/10.1007/s00018-013-1438-6
  50. Wiedenheft et al. (2011) RNA-guided complex from a bacterial immune system enhances target recognition through seed sequence interactions (pp. 10092-10097) https://doi.org/10.1073/pnas.1102716108
  51. Barrangou (2013) CRISPR/Cas systems and RNA-guided interference (pp. 267-278) https://doi.org/10.1002/wrna.1159
  52. Marraffini and Sontheimer (2010) CRISPR interference: RNA-directed adaptive immunity in bacteria and archaea (pp. 181-190) https://doi.org/10.1038/nrg2749
  53. Duan et al. (2021) Harnessing the CRISPR/Cas systems to combat antimicrobial resistance https://doi.org/10.3389/fmicb.2021.716064
  54. Uribe et al. (2021) Bacterial resistance to CRISPR/Cas antimicrobials https://doi.org/10.1038/s41598-021-96735-4
  55. Bikard and Barrangou (2017) Using CRISPR/Cas systems as antimicrobials (pp. 155-160) https://doi.org/10.1016/j.mib.2017.08.005
  56. Ramalingam and Thangavel (2019) CRISPR/Cas9 probing of infectious diseases and genetic disorders (pp. 1131-1135) https://doi.org/10.1007/s12098-019-03037-9
  57. Gholizadeh et al. (2017) Suppressing the CRISPR/Cas adaptive immune system in bacterial infections (pp. 2043-2051) https://doi.org/10.1007/s10096-017-3036-2
  58. Doerflinger et al. (2017) CRISPR/Cas9-the ultimate weapon to battle infectious diseases? https://doi.org/10.1111/cmi.12693
  59. Westerhout et al. (2005) HIV-1 can escape from RNA interference by evolving an alternative structure in its RNA genome (pp. 796-804) https://doi.org/10.1093/nar/gki220
  60. Xiao et al. (2019) Application of CRISPR/Cas9-based gene editing in HIV-1/AIDS therapy https://doi.org/10.3389/fcimb.2019.00069
  61. Wang et al. (2016) CRISPR/Cas9 can inhibit HIV-1 replication but NHEJ repair facilitates virus escape (pp. 522-526) https://doi.org/10.1038/mt.2016.24
  62. Das et al. (2019) Elimination of infectious HIV DNA by CRISPR/Cas9 (pp. 81-88) https://doi.org/10.1016/j.coviro.2019.07.001
  63. Lin et al. (2015) Application of CRISPR/Cas9 technology to HBV (pp. 26077-26086) https://doi.org/10.3390/ijms161125950
  64. Block et al. (2003) Molecular viral oncology of hepatocellular carcinoma (pp. 5093-5107) https://doi.org/10.1038/sj.onc.1206557
  65. Lee (1997) Hepatitis B virus infection (pp. 1733-1745) https://doi.org/10.1056/NEJM199712113372406
  66. Zeisel et al. (2015) Towards an HBV cure: state-of-the-art and unresolved questions–report of the ANRS workshop on HBV cure (pp. 1314-1326) https://doi.org/10.1136/gutjnl-2014-308943
  67. Ramanan et al. (2015) CRISPR/Cas9 cleavage of viral DNA efficiently suppresses hepatitis B virus https://doi.org/10.1038/srep10833
  68. Zhen et al. (2015) Harnessing the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated Cas9 system to disrupt the hepatitis B virus (pp. 404-412) https://doi.org/10.1038/gt.2015.2
  69. Li et al. (2017) Removal of integrated hepatitis B virus DNA using CRISPR/Cas9 https://doi.org/10.3389/fcimb.2017.00091
  70. McLaughlin-Drubin and Münger (2009) Oncogenic activities of human papillomaviruses (pp. 195-208) https://doi.org/10.1016/j.virusres.2009.06.008
  71. Hu Z, Yu L, Zhu D, et al. Disruption of HPV16-E7 by CRISPR/Cas system induces apoptosis and growth inhibition in HPV16 positive human cervical cancer cells. Biomed Res Int. 612823, (2014)
  72. Xu et al. (2021) Nanotechnology-based delivery of CRISPR/Cas9 for cancer treatment https://doi.org/10.1016/j.addr.2021.113891
  73. van Diemen, F.R., Lebbink, R.J.: CRISPR/Cas9, a powerful tool to target human herpesviruses. Cell Microbiol.
  74. 19
  75. (2017)
  76. Chen et al. (2018) Potential application of the CRISPR/Cas9 system against herpesvirus infections https://doi.org/10.3390/v10060291
  77. Nalawansha and Samarasinghe (2020) Double-barreled CRISPR technology as a novel treatment strategy for COVID-19 (pp. 790-800) https://doi.org/10.1021/acsptsci.0c00071
  78. Zetsche et al. (2015) Cpf1 is a single RNA-guided endonuclease of a class 2 CRISPR/Cas system (pp. 759-771) https://doi.org/10.1016/j.cell.2015.09.038
  79. Freije et al. (2019) Programmable inhibition and detection of RNA viruses using Cas13 (pp. 826-837) https://doi.org/10.1016/j.molcel.2019.09.013
  80. Konwarh (2020) Can CRISPR/Cas technology be a felicitous stratagem against the COVID-19 fiasco? Prospects and Hitches https://doi.org/10.3389/fmolb.2020.557377
  81. Tiwari et al. (2022) Antibacterial and antiviral high-performance nanosystems to mitigate new SARS-CoV-2 variants of concern https://doi.org/10.1016/j.cobme.2021.100363
  82. Yosef et al. (2015) Temperate and lytic bacteriophages programmed to sensitize and kill antibiotic-resistant bacteria (pp. 7267-7272) https://doi.org/10.1073/pnas.1500107112
  83. Loureiro and da Silva (2019) CRISPR/Cas: converting a bacterial defence mechanism into a state-of-the-art genetic manipulation tool https://doi.org/10.3390/antibiotics8010018
  84. Griffith (1928) The significance of pneumococcal types (pp. 113-159) https://doi.org/10.1017/S0022172400031879
  85. Avery et al. (1944) Studies on the chemical nature of the substance inducing transformation of pneumococcal types: induction of transformation by a desoxyribonucleic acid fraction isolated from pneumococcus type III (pp. 137-158) https://doi.org/10.1084/jem.79.2.137
  86. Bikard et al. (2012) CRISPR interference can prevent natural transformation and virulence acquisition during in vivo bacterial infection (pp. 177-186) https://doi.org/10.1016/j.chom.2012.06.003
  87. Zumla et al. (2013) Fordham von Reyn C Tuberculosis (pp. 745-755) https://doi.org/10.1056/NEJMra1200894
  88. Choudhary et al. (2015) Gene silencing by CRISPR interference in mycobacteria https://doi.org/10.1038/ncomms7267
  89. Singh et al. (2016) Investigating essential gene function in Mycobacterium tuberculosis using an efficient CRISPR interference system https://doi.org/10.1093/nar/gkw625
  90. Cady et al. (2012) The CRISPR/Cas adaptive immune system of Pseudomonas aeruginosa mediates resistance to naturally occurring and engineered phages (pp. 5728-5738) https://doi.org/10.1128/JB.01184-12
  91. Wheatley and MacLean (2021) CRISPR/Cas systems restrict horizontal gene transfer in Pseudomonas aeruginosa (pp. 1420-1433) https://doi.org/10.1038/s41396-020-00860-3
  92. Citorik et al. (2014) Sequence-specific antimicrobials using efficiently delivered RNA-guided nucleases (pp. 1141-1145) https://doi.org/10.1038/nbt.3011
  93. Gomaa et al. (2014) Programmable removal of bacterial strains by use of genome-targeting CRISPR/Cas systems (pp. e00928-e1013) https://doi.org/10.1128/mBio.00928-13
  94. DiCarlo et al. (2013) Genome engineering in Saccharomyces cerevisiae using CRISPR/Cas systems (pp. 4336-4343) https://doi.org/10.1093/nar/gkt135
  95. Wang and Coleman (2019) Progress and challenges: development and implementation of CRISPR/Cas9 technology in filamentous fungi (pp. 761-769) https://doi.org/10.1016/j.csbj.2019.06.007
  96. Liu et al. (2015) Efficient genome editing in filamentous fungus Trichoderma reesei using the CRISPR/Cas9 system https://doi.org/10.1038/celldisc.2015.7
  97. Morio et al. (2020) The CRISPR toolbox in medical mycology: state of the art and perspectives https://doi.org/10.1371/journal.ppat.1008201
  98. Fuller et al. (2015) Development of the CRISPR/Cas9 system for targeted gene disruption in Aspergillus fumigatus (pp. 1073-1080) https://doi.org/10.1128/EC.00107-15
  99. Krappmann (2017) CRISPR/Cas9, the new kid on the block of fungal molecular biology (pp. 16-23) https://doi.org/10.1093/mmy/myw097
  100. Vyas et al. (2015) A Candida albicans CRISPR system permits genetic engineering of essential genes and gene families https://doi.org/10.1126/sciadv.1500248
  101. Shanmugam et al. (2019) The CRISPR/Cas9 system for targeted genome engineering in free-living fungi: advances and opportunities for lichenized fungi https://doi.org/10.3389/fmicb.2019.00062
  102. Arras et al. (2016) Targeted genome editing via CRISPR in the pathogen Cryptococcus neoformans https://doi.org/10.1371/journal.pone.0164322
  103. van den Brink et al. (2013) Efficient plant biomass degradation by thermophilic fungus Myceliophthora heterothallica (pp. 1316-1324) https://doi.org/10.1128/AEM.02865-12
  104. Liu et al. (2017) Development of a genome-editing CRISPR/Cas9 system in thermophilic fungal Myceliophthora species and its application to hyper-cellulase production strain engineering https://doi.org/10.1186/s13068-016-0693-9
  105. Ribes et al. (2000) Zygomycetes in human disease (pp. 236-301) https://doi.org/10.1128/CMR.13.2.236
  106. Arroyo MA, Schmitt BH, Davis TE, Relich RF. Detection of the dimorphic phases of mucor circinelloides in blood cultures from an immunosuppressed female. Case Rep. Infect. Dis. 3720549 (2016)
  107. Bruni et al. (2019) CRISPR/Cas9 induces point mutation in the mucormycosis fungus Rhizopus delemar (pp. 1-7) https://doi.org/10.1016/j.fgb.2018.12.002
  108. Nagy et al. (2017) Development of a plasmid free CRISPR/Cas9 system for the genetic modification of Mucor circinelloides https://doi.org/10.1038/s41598-017-17118-2
  109. Kumar et al. (2021) Aspects of point-of-care diagnostics for personalized health wellness (pp. 383-402) https://doi.org/10.2147/IJN.S267212
  110. Wang et al. (2020) Next-generation pathogen diagnosis with CRISPR/Cas-based detection methods (pp. 1682-1691) https://doi.org/10.1080/22221751.2020.1793689
  111. Zhao et al. (2015) Isothermal amplification of nucleic acids (pp. 12491-12545) https://doi.org/10.1021/acs.chemrev.5b00428
  112. Kaushik et al. (2020) Electrochemical sars-cov-2 sensing at point-of-care and artificial intelligence for intelligent covid-19 management (pp. 7306-7325) https://doi.org/10.1021/acsabm.0c01004
  113. Chen et al. (2021) Point-of-care CRISPR/Cas-assisted SARS-CoV-2 detection in an automated and portable droplet magnetofluidic device https://doi.org/10.1016/j.bios.2021.113390
  114. Paliwal, P., Sargolzaei, S., Bhardwaj, S.K., Bhardwaj, V., Dixit, C., Kaushik, A.: Grand challenges in bio-nanotechnology to manage the covid-19 pandemic. Front. Nanotech.
  115. 2
  116. (2020)
  117. Jain et al. (2021) Internet of medical things (IoMT)-integrated biosensors for point-of-care testing of infectious diseases https://doi.org/10.1016/j.bios.2021.113074
  118. Kaushik (2021) Manipulative magnetic nanomedicine: the future of COVID-19 pandemic/endemic therapy (pp. 531-534) https://doi.org/10.1080/17425247.2021.1860938
  119. Yuen et al. (2018) Suppression of Epstein-Barr virus DNA load in latently infected nasopharyngeal carcinoma cells by CRISPR/Cas9 (pp. 296-303) https://doi.org/10.1016/j.virusres.2017.04.019
  120. Chertow (2018) Next-generation diagnostics with CRISPR (pp. 381-382) https://doi.org/10.1126/science.aat4982
  121. Chiu (2018) Cutting-edge infectious disease diagnostics with CRISPR (pp. 702-704) https://doi.org/10.1016/j.chom.2018.05.016
  122. Pardee et al. (2016) Rapid, low-cost detection of zika virus using programmable biomolecular components (pp. 1255-1266) https://doi.org/10.1016/j.cell.2016.04.059
  123. Xiang et al. (2020) CRISPR/Cas systems based molecular diagnostic tool for infectious diseases and emerging 2019 novel coronavirus (COVID-19) pneumonia (pp. 727-731) https://doi.org/10.1080/1061186X.2020.1769637
  124. Uppada et al. (2018) Diagnosis and therapy with CRISPR advanced CRISPR based tools for point of care diagnostics and early therapies (pp. 22-29) https://doi.org/10.1016/j.gene.2018.02.066
  125. Wang et al. (2016) CRISPR/Cas9-derived mutations both inhibit HIV-1 replication and accelerate viral escape (pp. 481-489) https://doi.org/10.1016/j.celrep.2016.03.042
  126. Tian et al. (2019) CRISPR/Cas9—an evolving biological tool kit for cancer biology and oncology https://doi.org/10.1038/s41698-019-0080-7
  127. Hajian et al. (2019) Detection of unamplified target genes via CRISPR/Cas9 immobilized on a graphene field-effect transistor (pp. 427-437) https://doi.org/10.1038/s41551-019-0371-x
  128. Bruch et al. (2019) Unamplified gene sensing via Cas9 on graphene (pp. 419-420) https://doi.org/10.1038/s41551-019-0413-4
  129. Cordaro et al. (2020) Graphene-based strategies in liquid biopsy and in viral diseases diagnosis https://doi.org/10.3390/nano10061014
  130. Quan et al. (2019) FLASH: a next-generation CRISPR diagnostic for multiplexed detection of antimicrobial resistance sequences https://doi.org/10.1093/nar/gkz418
  131. Srivastava et al. (2020) Next-generation molecular diagnostics development by CRISPR/Cas tool: rapid detection and surveillance of viral disease outbreaks https://doi.org/10.3389/fmolb.2020.582499
  132. Zhou et al. (2018) A CRISPR/Cas9-triggered strand displacement amplification method for ultrasensitive DNA detection https://doi.org/10.1038/s41467-018-07324-5
  133. Huang et al. (2018) Clustered regularly interspaced short palindromic repeats/Cas9 triggered isothermal amplification for site-specific nucleic acid detection (pp. 2193-2200) https://doi.org/10.1021/acs.analchem.7b04542
  134. Jia et al. (2020) The expanded development and application of CRISPR system for sensitive nucleotide detection (pp. 624-629) https://doi.org/10.1007/s13238-020-00708-8
  135. Field et al. (2018) DNA methylation clocks in aging: categories, causes, and consequences (pp. 882-895) https://doi.org/10.1016/j.molcel.2018.08.008
  136. Wang et al. (2020) Clustered regularly interspaced short palindromic repeats/Cas9-mediated lateral flow nucleic acid assay (pp. 2497-2508) https://doi.org/10.1021/acsnano.0c00022
  137. van Dongen et al. (2020) Point-of-care CRISPR/Cas nucleic acid detection: recent advances, challenges and opportunities https://doi.org/10.1016/j.bios.2020.112445
  138. Azhar M, Phutela R, Ansari AH, et al. Rapid, field-deployable nucleobase detection and identification using FnCas9. biorxiv. 2020.
  139. Chen et al. (2018) CRISPR/Cas12a target binding unleashes indiscriminate single-stranded DNase activity (pp. 436-439) https://doi.org/10.1126/science.aar6245
  140. Li et al. (2018) CRISPR/Cas12a-assisted nucleic acid detection https://doi.org/10.1038/s41421-018-0028-z
  141. Rusk (2019) Spotlight on Cas12 https://doi.org/10.1038/s41592-019-0347-5
  142. Paul and Montoya (2020) CRISPR/Cas12a: Functional overview and applications (pp. 8-17) https://doi.org/10.1016/j.bj.2019.10.005
  143. Kocak and Gersbach (2018) From CRISPR scissors to virus sensors (pp. 168-169) https://doi.org/10.1038/d41586-018-04975-8
  144. Murugan et al. (2020) CRISPR/Cas12a has widespread off-target and dsDNA-nicking effects (pp. 5538-5553) https://doi.org/10.1074/jbc.RA120.012933
  145. Huang et al. (2020) Ultra-sensitive and high-throughput CRISPR-powered COVID-19 diagnosis https://doi.org/10.1016/j.bios.2020.112316
  146. Palaz et al. (2021) CRISPR-based tools: alternative methods for the diagnosis of COVID-19 (pp. 1-13) https://doi.org/10.1016/j.clinbiochem.2020.12.011
  147. Xu et al. (2020) An isothermal method for sensitive detection of mycobacterium tuberculosis complex using clustered regularly interspaced short palindromic repeats/Cas12a Cis and trans cleavage (pp. 1020-1029) https://doi.org/10.1016/j.jmoldx.2020.04.212
  148. Kumar et al. (2020) CRISPR/Cas system: an approach with potentials for COVID-19 diagnosis and therapeutics https://doi.org/10.3389/fcimb.2020.576875
  149. Ding, X, Yin, K, Li, Z, Liu, C.: All-in-One Dual CRISPR/Cas12a (AIOD-CRISPR) assay: a case for rapid, ultrasensitive and visual detection of novel coronavirus SARS-CoV-2 and HIV virus. BioRxiv. 2020.03.19.998724 (2020).
  150. Phan et al. (2022) CRISPR/Cas-powered nanobiosensors for diagnostics https://doi.org/10.1016/j.bios.2021.113732
  151. Choi et al. (2021) CRISPR/Cas12a-based nucleic acid amplification-free DNA biosensor via Au nanoparticle-assisted metal-enhanced fluorescence and colorimetric analysis (pp. 693-699) https://doi.org/10.1021/acs.nanolett.0c04303
  152. Lee et al. (2020) Ultrasensitive CRISPR-based diagnostic for field-applicable detection of Plasmodium species in symptomatic and asymptomatic malaria (pp. 25722-25731) https://doi.org/10.1073/pnas.2010196117
  153. Nouri et al. (2020) Sequence-specific recognition of HIV-1 DNA with solid-state CRISPR/Cas12a-assisted nanopores (SCAN) (pp. 1273-1280) https://doi.org/10.1021/acssensors.0c00497
  154. Shao et al. (2019) CRISPR/Cas12a coupled with platinum nanoreporter for visual quantification of SNVs on a volumetric bar-chart chip (pp. 12384-12391) https://doi.org/10.1021/acs.analchem.9b02925
  155. Abudayyeh et al. (2016) C2c2 is a single-component programmable RNA-guided RNA-targeting CRISPR effector https://doi.org/10.1126/science.aaf5573
  156. Gootenberg et al. (2017) Nucleic acid detection with CRISPR/Cas13a/C2c2 (pp. 438-442) https://doi.org/10.1126/science.aam9321
  157. Kellner et al. (2019) SHERLOCK: nucleic acid detection with CRISPR nucleases (pp. 2986-3012) https://doi.org/10.1038/s41596-019-0210-2
  158. Tsou et al. (2019) A CRISPR test for detection of circulating nuclei acids (pp. 1566-1573) https://doi.org/10.1016/j.tranon.2019.08.011
  159. Sashital (2018) Pathogen detection in the CRISPR/Cas era https://doi.org/10.1186/s13073-018-0543-4
  160. Shihong Gao et al. (2021) Development and application of sensitive, specific, and rapid CRISPR/Cas13-based diagnosis (pp. 4198-4204) https://doi.org/10.1002/jmv.26889
  161. Liu et al. (2019) CRISPR/Cas13a nanomachine based simple technology for avian influenza A (H7N9) virus on-site detection (pp. 790-798) https://doi.org/10.1166/jbn.2019.2742
  162. Bruch et al. (2019) CRISPR/cas13a-powered electrochemical microfluidic biosensor for nucleic acid amplification-free MIRNA diagnostics https://doi.org/10.1002/adma.201905311
  163. Ibrahim et al. (2020) Futuristic CRISPR-based biosensing in the cloud and internet of things era: an overview (pp. 1-29)
  164. Sheng et al. (2021) A CRISPR/Cas13a-powered catalytic electrochemical biosensor for successive and highly sensitive RNA diagnostics https://doi.org/10.1016/j.bios.2021.113027
  165. Myhrvold et al. (2018) Field-deployable viral diagnostics using CRISPR/Cas13 (pp. 444-448) https://doi.org/10.1126/science.aas8836
  166. Chotiwan et al. (2017) Rapid and specific detection of Asian- and African-lineage Zika viruses https://doi.org/10.1126/scitranslmed.aag0538
  167. Chen et al. (2019) Invited review: Advancements in lateral flow immunoassays for screening hazardous substances in milk and milk powder (pp. 1887-1900) https://doi.org/10.3168/jds.2018-15462
  168. Khambhati et al. (2019) Current progress in CRISPR-based diagnostic platforms (pp. 2721-2725) https://doi.org/10.1002/jcb.27690
  169. Lyu et al. (2020) CRISPR-based biosensing is prospective for rapid and sensitive diagnosis of pediatric tuberculosis (pp. 183-187) https://doi.org/10.1016/j.ijid.2020.09.1428
  170. Hu et al. (2020) Single-step, salt-aging-free, and thiol-free freezing construction of AuNP-based bioprobes for advancing CRISPR-based diagnostics (pp. 7506-7513) https://doi.org/10.1021/jacs.0c00217
  171. Karvelis et al. (2020) PAM recognition by miniature CRISPR/Cas12f nucleases triggers programmable double-stranded DNA target cleavage (pp. 5016-5023) https://doi.org/10.1093/nar/gkaa208
  172. Harrington et al. (2018) Programmed DNA destruction by miniature CRISPR/Cas14 enzymes (pp. 839-842) https://doi.org/10.1126/science.aav4294
  173. Aquino-Jarquin (2019) CRISPR/Cas14 is now part of the artillery for gene editing and molecular diagnostic (pp. 428-431) https://doi.org/10.1016/j.nano.2019.03.006
  174. Vatankhah et al. (2021) CRISPR-based biosensing systems: a way to rapidly diagnose COVID-19 (pp. 225-241) https://doi.org/10.1080/10408363.2020.1849010
  175. Global health estimates. World Health Organization.
  176. https://www.who.int/data/global-health-estimates
  177. . Accessed 10 Sept (2021).
  178. Zaychikova et al. (2020) CRISPR/Cas systems: prospects for use in medicine https://doi.org/10.3390/app10249001
  179. Vashist et al. (2016) Recent trends on hydrogel-based drug delivery systems for infectious diseases (pp. 1535-1553) https://doi.org/10.1039/C6BM00276E
  180. Yin et al. (2015) The application of CRISPR-Cas9 gene editing technology in viral infection diseases (pp. 412-418)
  181. Kim et al. (2020) Nanovesicle-mediated delivery systems for CRISPR/Cas genome editing https://doi.org/10.3390/pharmaceutics12121233
  182. Wu et al. (2010) Effect of genome size on AAV vector packaging (pp. 80-86) https://doi.org/10.1038/mt.2009.255
  183. Elmowafy et al. (2019) Biocompatibility, biodegradation and biomedical applications of poly (lactic acid)/poly (lactic-co-glycolic acid) micro and nanoparticles (pp. 347-380) https://doi.org/10.1007/s40005-019-00439-x
  184. Lyu et al. (2021) Active delivery of CRISPR system using targetable or controllable nanocarriers https://doi.org/10.1002/smll.202005222
  185. Ramakrishna et al. (2014) Gene disruption by cell-penetrating peptide-mediated delivery of Cas9 protein and guide RNA (pp. 1020-1027) https://doi.org/10.1101/gr.171264.113
  186. Gage A, Brunson K, Morris K, et al. Perspectives of manipulative and high-performance nanosystems to manage consequences of emerging new severe acute respiratory syndrome coronavirus 2 variants. Front. Nanotechnol.
  187. 3
  188. . (2021)
  189. Bhardwaj et al. (2019) Recalcitrant issues and new frontiers in nano-pharmacology https://doi.org/10.3389/fphar.2019.01369
  190. Ortiz-Casas et al. (2021) Bio-acceptable 0d and 1d ZnO nanostructures for cancer diagnostics and treatment (pp. 533-569) https://doi.org/10.1016/j.mattod.2021.07.025
  191. Wilbie et al. (2019) Delivery aspects of CRISPR/Cas for in vivo genome editing (pp. 1555-1564) https://doi.org/10.1021/acs.accounts.9b00106
  192. Thi et al. (2017) siRNA rescues nonhuman primates from advanced Marburg and Ravn virus disease (pp. 4437-4448) https://doi.org/10.1172/JCI96185
  193. Jayant et al. (2016) Current status of Non-viral gene therapy for CNS disorders (pp. 1433-1445) https://doi.org/10.1080/17425247.2016.1188802
  194. Givens et al. (2018) Nanoparticle-based delivery of CRISPR/Cas9 genome-editing therapeutics https://doi.org/10.1208/s12248-018-0267-9
  195. Zhang L, Wang P, Feng Q, et al. Lipid nanoparticle-mediated efficient delivery of Crispr/cas9 for tumor therapy. NPG Asia Mater.
  196. 9
  197. (2017).
  198. Mukalel et al. (2019) Nanoparticles for nucleic acid delivery: applications in cancer immunotherapy (pp. 102-112) https://doi.org/10.1016/j.canlet.2019.04.040
  199. Barman et al. (2020) CRISPR/Cas9: a promising genome editing therapeutic tool for Alzheimer's disease-a narrative review (pp. 419-434) https://doi.org/10.1007/s40120-020-00218-z
  200. Sheridan (2017) CRISPR therapeutics push into human testing (pp. 3-5) https://doi.org/10.1038/nbt0117-3
  201. Norgren et al. (2014) Gene expression profile in hereditary transthyretin amyloidosis: differences in targeted and source organs (pp. 113-119) https://doi.org/10.3109/13506129.2014.894908
  202. Park et al. (2019) In vivo neuronal gene editing via CRISPR/Cas9 amphiphilic nanocomplexes alleviates deficits in mouse models of Alzheimer's disease (pp. 524-528) https://doi.org/10.1038/s41593-019-0352-0
  203. Kennedy et al. (2014) Inactivation of the human papillomavirus E6 or E7 gene in cervical carcinoma cells by using a bacterial CRISPR/Cas RNA-guided endonuclease (pp. 11965-11972) https://doi.org/10.1128/JVI.01879-14
  204. Cho et al. (2019) Lecithin nano-liposomal particle as a CRISPR/Cas9 complex delivery system for treating type 2 diabetes https://doi.org/10.1186/s12951-019-0452-8
  205. Xu et al. (2019) Development of “CLAN” nanomedicine for nucleic acid therapeutics https://doi.org/10.1002/smll.201900055
  206. Yin et al. (2016) Therapeutic genome editing by combined viral and non-viral delivery of CRISPR system components in vivo (pp. 328-333) https://doi.org/10.1038/nbt.3471
  207. Finn et al. (2018) A single administration of CRISPR/Cas9 lipid nanoparticles achieves robust and persistent in vivo genome editing (pp. 2227-2235) https://doi.org/10.1016/j.celrep.2018.02.014
  208. Chuang et al. (2021) Approach for in vivo delivery of CRISPR/Cas system: a recent update and future prospect (pp. 2683-2708) https://doi.org/10.1007/s00018-020-03725-2
  209. Liu et al. (2019) Fast and efficient CRISPR/Cas9 genome editing in vivo enabled by bioreducible lipid and messenger RNA nanoparticles https://doi.org/10.1002/adma.201902575
  210. Senyei et al. (1978) Magnetic guidance of drug carrying microspheres (pp. 3578-3583) https://doi.org/10.1063/1.325219
  211. Widder et al. (1978) Magnetic microspheres: a model system of site-specific drug delivery in vivo (pp. 141-146) https://doi.org/10.3181/00379727-158-40158
  212. McBain et al. (2008) Magnetic nanoparticles for gene and drug delivery (pp. 169-180)
  213. Tang et al. (2021) Synthetic multi-layer nanoparticles for CRISPR/Cas9 genome editing (pp. 55-78) https://doi.org/10.1016/j.addr.2020.03.001
  214. Babačić et al. (2019) CRISPR/Cas gene-editing as plausible treatment of neuromuscular and nucleotide-repeat-expansion diseases: a systematic review https://doi.org/10.1371/journal.pone.0212198
  215. Shahbazi et al. (2019) Targeted homology-directed repair in blood stem and progenitor cells with CRISPR nanoformulations (pp. 1124-1132) https://doi.org/10.1038/s41563-019-0385-5
  216. Alagoz and Kherad (2020) Advance genome editing technologies in the treatment of human diseases: CRISPR therapy (Review) (pp. 521-534) https://doi.org/10.3892/ijmm.2020.4609
  217. Lee et al. (2018) Nanoparticle delivery of CRISPR into the brain rescues a mouse model of fragile X syndrome from exaggerated repetitive behaviours (pp. 497-507) https://doi.org/10.1038/s41551-018-0252-8
  218. Tay et al. (2020) Translating CRISPR/Cas therapeutics: approaches and challenges (pp. 253-275) https://doi.org/10.1089/crispr.2020.0025
  219. Yue et al. (2018) Graphene oxide-mediated Cas9/sgRNA delivery for efficient genome editing (pp. 1063-1071) https://doi.org/10.1039/C7NR07999K
  220. Liu et al. (2013) Graphene and graphene oxide as new nanocarriers for drug delivery applications (pp. 9243-9257) https://doi.org/10.1016/j.actbio.2013.08.016
  221. Imani et al. (2018) Graphene-based Nano-Carrier modifications for gene delivery applications (pp. 569-591) https://doi.org/10.1016/j.carbon.2018.09.019
  222. Hryhorowicz et al. (2019) Improved delivery of CRISPR/Cas9 system using magnetic nanoparticles into porcine fibroblast (pp. 173-180) https://doi.org/10.1007/s12033-018-0145-9
  223. Kaushik et al. (2019) Magnetically guided non-invasive CRISPR/Cas9/gRNA delivery across blood-brain barrier to eradicate latent HIV-1 infection https://doi.org/10.1038/s41598-019-40222-4
  224. Nehra et al. (2021) Nanobiotechnology-assisted therapies to manage brain cancer in personalized manner (pp. 224-243) https://doi.org/10.1016/j.jconrel.2021.08.027
  225. Sadique et al. (2021) High-performance antiviral nano-systems as a shield to inhibit viral infections: SARS-CoV-2 as a model case study (pp. 4620-4642) https://doi.org/10.1039/D1TB00472G
  226. Varahachalam et al. (2021) Nanomedicine for the SARS-CoV-2: state-of-the-art and future prospects (pp. 539-560) https://doi.org/10.2147/IJN.S283686
  227. Kaushik, A., Nikkhah-Moshaie, R., Sinha, R., Bhardwaj, V., Atluri, V., Jayant, R.D., Yndart, A., Kateb, B., Pala, N., Nair, M.: Investigation of AC-magnetic field stimulated nanoelectroporation of magneto-electric nano-drug-carrier inside CNS cells. Sci. Rep.
  228. 7
  229. , (2017).
  230. Kaushik, A., Jayant, R.D., Nikkhah-Moshaie, R., Bhardwaj, V., Roy, U., Huang, Z., Ruiz, A., Yndart, A., Atluri, V., El-Hage, N., Khalili, K., Nair, M.: Magnetically guided central nervous system delivery and toxicity evaluation of magneto-electric nanocarriers. Sci. Rep.
  231. 6
  232. , (2016).
  233. Kaushik et al. (2019) MRI-guided, noninvasive delivery of magneto-electric drug nanocarriers to the brain in a nonhuman primate (pp. 4826-4836) https://doi.org/10.1021/acsabm.9b00592
  234. Dizaj et al. (2014) A sight on the current nanoparticle-based gene delivery vectors https://doi.org/10.1186/1556-276X-9-252
  235. Kumar et al. (2020) Core-shell nanostructures: perspectives towards drug delivery applications (pp. 8992-9027) https://doi.org/10.1039/D0TB01559H
  236. Glass et al. (2018) Engineering the delivery system for CRISPR-based genome editing (pp. 173-185) https://doi.org/10.1016/j.tibtech.2017.11.006
  237. Wang et al. (2018) Nonviral gene editing via CRISPR/Cas9 delivery by membrane-disruptive and endosomolytic helical polypeptide (pp. 4903-4908) https://doi.org/10.1073/pnas.1712963115
  238. Liu et al. (2018) Optimization of lipid-assisted nanoparticle for disturbing neutrophils-related inflammation (pp. 92-104) https://doi.org/10.1016/j.biomaterials.2018.04.052
  239. Rui et al. (2020) Poly (Beta-Amino Ester) nanoparticles enable nonviral delivery of CRISPR/Cas9 plasmids for gene knockout and gene deletion (pp. 661-672) https://doi.org/10.1016/j.omtn.2020.04.005
  240. Jo et al. (2020) Fabrication and characterization of PLGA nanoparticles encapsulating large CRISPR/Cas9 plasmid https://doi.org/10.1186/s12951-019-0564-1
  241. Timin et al. (2018) Efficient gene editing via non-viral delivery of CRISPR/Cas9 system using polymeric and hybrid microcarriers (pp. 97-108) https://doi.org/10.1016/j.nano.2017.09.001
  242. Sun et al. (2015) Self-assembled DNA nanoclews for the efficient delivery of CRISPR/Cas9 for genome editing (pp. 12029-12033) https://doi.org/10.1002/anie.201506030
  243. Luther et al. (2018) Delivery approaches for CRISPR/Cas9 therapeutics in vivo: advances and challenges (pp. 905-913) https://doi.org/10.1080/17425247.2018.1517746
  244. Chen et al. (2014) Zeolitic imidazolate framework materials: recent progress in synthesis and applications (pp. 16811-16831) https://doi.org/10.1039/C4TA02984D
  245. Eoh and Gu (2019) Biomaterials as vectors for the delivery of CRISPR/Cas9 (pp. 1240-1261) https://doi.org/10.1039/C8BM01310A
  246. Ju et al. (2019) Gold nanocluster-mediated efficient delivery of Cas9 protein through pH-induced assembly-disassembly for inactivation of virus oncogenes (pp. 34717-34724) https://doi.org/10.1021/acsami.9b12335
  247. Ebina et al. (2013) Harnessing the CRISPR/Cas9 system to disrupt latent HIV-1 provirus https://doi.org/10.1038/srep02510
  248. Rabiee, N., Bagherzadeh, M., Ghadiri, A. M., Kiani, M., Ahmadi, S., Jajarmi, V., Fatahi, Y., Aldhaher, A., Tahriri, M., Webster, T. J., Mostafavi, E.: Calcium-based nanomaterials and their interrelation with chitosan: optimization for pCRISPR delivery. J. Nanostruct. Chem., 1–14 (2021).
  249. Lostalé-Seijo et al. (2017) Peptide/Cas9 nanostructures for ribonucleoprotein cell membrane transport and gene edition (pp. 7923-7931) https://doi.org/10.1039/C7SC03918B
  250. Lin et al. (2018) Exosome-liposome hybrid nanoparticles deliver CRISPR/Cas9 system in MSCs https://doi.org/10.1002/advs.201700611
  251. Khunger et al. (2021) Perspective and prospects of 2D MXenes for smart biosensing https://doi.org/10.1016/j.matlet.2021.130656
  252. Zuris et al. (2015) Cationic lipid-mediated delivery of proteins enables efficient protein-based genome editing in vitro and in vivo (pp. 73-80) https://doi.org/10.1038/nbt.3081
  253. Mangeot et al. (2019) Genome editing in primary cells and in vivo using viral-derived Nanoblades loaded with Cas9-sgRNA ribonucleoproteins https://doi.org/10.1038/s41467-018-07845-z
  254. Dong et al. (2013) MicroRNA: function, detection, and bioanalysis (pp. 6207-6233) https://doi.org/10.1021/cr300362f
  255. Wang et al. (2020) CRISPR/cas systems redefine nucleic acid detection: principles and methods https://doi.org/10.1016/j.bios.2020.112430
  256. Staahl et al. (2017) Efficient genome editing in the mouse brain by local delivery of engineered Cas9 ribonucleoprotein complexes (pp. 431-434) https://doi.org/10.1038/nbt.3806
  257. Wagner et al. (2021) Cas9-directed immune tolerance in humans-a model to evaluate regulatory T cells in gene therapy? (pp. 549-559) https://doi.org/10.1038/s41434-021-00232-2
  258. Mout et al. (2017) Direct cytosolic delivery of CRISPR/Cas9-ribonucleoprotein for efficient gene editing (pp. 2452-2458) https://doi.org/10.1021/acsnano.6b07600
  259. Kedmi et al. (2010) The systemic toxicity of positively charged lipid nanoparticles and the role of Toll-like receptor 4 in immune activation (pp. 6867-6875) https://doi.org/10.1016/j.biomaterials.2010.05.027
  260. Reichmuth et al. (2016) mRNA vaccine delivery using lipid nanoparticles (pp. 319-334) https://doi.org/10.4155/tde-2016-0006
  261. Ferdosi et al. (2019) Multifunctional CRISPR/Cas9 with engineered immunosilenced human T cell epitopes https://doi.org/10.1038/s41467-019-09693-x
  262. Wagner et al. (2019) High prevalence of Streptococcus pyogenes Cas9-reactive T cells within the adult human population (pp. 242-248) https://doi.org/10.1038/s41591-018-0204-6
  263. Xiao et al. (2021) Extensive adaptive immune response of Aavs and Cas proteins in non-human primates (pp. 2061-2064) https://doi.org/10.1016/j.scib.2021.02.009
  264. Fu et al. (2013) High-frequency off-target mutagenesis induced by CRISPR/Cas nucleases in human cells (pp. 822-826) https://doi.org/10.1038/nbt.2623
  265. Xu and Li (2020) CRISPR/Cas systems: overview, innovations and applications in human disease research and gene therapy (pp. 2401-2415) https://doi.org/10.1016/j.csbj.2020.08.031
  266. Slaymaker et al. (2016) Rationally engineered Cas9 nucleases with improved specificity (pp. 84-88) https://doi.org/10.1126/science.aad5227
  267. Kleinstiver et al. (2016) High-fidelity CRISPR/Cas9 nucleases with no detectable genome-wide off-target effects (pp. 490-495) https://doi.org/10.1038/nature16526
  268. Sahel et al. (2019) CRISPR/Cas system for genome editing: progress and prospects as a therapeutic tool (pp. 725-735) https://doi.org/10.1124/jpet.119.257287
  269. Nayak and Herzog (2010) Progress and prospects: immune responses to viral vectors (pp. 295-304) https://doi.org/10.1038/gt.2009.148
  270. Mout et al. (2017) In vivo delivery of CRISPR/Cas9 for therapeutic gene editing: progress and challenges (pp. 880-884) https://doi.org/10.1021/acs.bioconjchem.7b00057
  271. Mishra et al. (2004) PEGylation significantly affects cellular uptake and intracellular trafficking of non-viral gene delivery particles (pp. 97-111) https://doi.org/10.1078/0171-9335-00363
  272. Charlesworth et al. (2019) Identification of pre-existing adaptive immunity to Cas9 proteins in humans (pp. 249-254) https://doi.org/10.1038/s41591-018-0326-x
  273. Misra, C.S., Bindal, G., Sodani, M., et al.: Determination of cas9/dcas9 associated toxicity in microbes. BioRxiv. 848135 (2019).
  274. Nair et al. (2016) Getting into the brain: potential of nanotechnology in the management of NeuroAIDS (pp. 202-217) https://doi.org/10.1016/j.addr.2016.02.008
  275. Sharma et al. (2021) Ultrasensitive and reusable graphene oxide-modified double-interdigitated capacitive (DIDC) sensing chip for detecting SARS-CoV-2 (pp. 3468-3476) https://doi.org/10.1021/acssensors.1c01437
  276. Morales-Narváez and Dincer (2020) The impact of biosensing in a pandemic outbreak: Covid-19 https://doi.org/10.1016/j.bios.2020.112274
  277. Jansen et al. (2002) Identification of genes that are associated with DNA repeats in prokaryotes (pp. 1565-1575) https://doi.org/10.1046/j.1365-2958.2002.02839.x