Utilizing CRISPR Technology to Develop Vaccinations and Treatments Against Viruses

Samaa Faez  Khudhur

doi:10.51699/cajmns.v7i2.3148

Authors

Samaa Faez Khudhur Faculty of science, University of Thi-Qar, Iraq

DOI:

https://doi.org/10.51699/cajmns.v7i2.3148

Keywords:

CRISPR-Cas Gene editing, Infection, Treatment Virus

Abstract

CRISPR/Cas systems have attracted considerable attention because of their ability to detect and eliminate foreign nucleic acid, DNA and Genes; most amazingly, this type of process is also present within human cells here on Earth. It is like a system that has obtained immunity, such as this development over time. The recent discovery that CRISPR/Cas 9, 12 and 13 systems can be artificially altered leads to a new potential. The target of these altered systems is human diseases: DNA and RNA viruses. Current methods of prevention and treatment cannot deal with the RNA virus that caused the 2019 coronavirus pandemic, a serious public health concern. The CRISPR /Cas system offers a useful approach to gene editing in comparison with traditional techniques for managing viral infections. This comprehensive review summarizes the latest strategies for treating and preventing human viral infection via CRISPR/Cas technology. We also identify significant challenges and look to a hopeful future for this cutting-edge gene editing method.

References

A. Qureshi, V. G. Tantray, A. R. Kirmani, and A. G. Ahangar, “A review on current status of antiviral siRNA,” Rev. Med. Virol., vol. 28, 2018, Art. no. e1976, doi: 10.1002/rmv.1976.

B. Hu, H. Guo, P. Zhou, and Z.-L. Shi, “Characteristics of SARS-CoV-2 and COVID-19,” Nat. Rev. Microbiol., vol. 19, pp. 141–154, 2021, doi: 10.1038/s41579-020-00459-7.

D. Skegg et al., “Future scenarios for the COVID-19 pandemic,” Lancet, vol. 397, pp. 777–778, 2021, doi: 10.1016/S0140-6736(21)00424-4.

R. L. Hamers, T. F. Rinke de Wit, and C. B. Holmes, “HIV drug resistance in low-income and middle-income countries,” Lancet HIV, vol. 5, pp. e588–e596, 2018, doi: 10.1016/S2352-3018(18)30173-5.

L. S. Y. Tang, E. Covert, E. Wilson, and S. Kottilil, “Chronic hepatitis B infection: A review,” JAMA, vol. 319, pp. 1802–1813, 2018, doi: 10.1001/jama.2018.3795.

J. C. Rotondo et al., “Epigenetic dysregulations in Merkel cell polyomavirus-driven Merkel cell carcinoma,” Int. J. Mol. Sci., vol. 22, 2021, Art. no. 11464, doi: 10.3390/ijms222111464.

A. Mehta, T. Michler, and O. M. Merkel, “siRNA therapeutics against respiratory viral infections—what have we learned for potential COVID-19 therapies?” Adv. Healthc. Mater., vol. 10, 2021, Art. no. 2001650, doi: 10.1002/adhm.202001650.

A. Adalja and T. Inglesby, “Broad-spectrum antiviral agents: A crucial pandemic tool,” Expert Rev. Anti Infect. Ther., vol. 17, pp. 467–470, 2019, doi: 10.1080/14787210.2019.1635009.

A. Levanova and M. M. Poranen, “RNA interference as a prospective tool for the control of human viral infections,” Front. Microbiol., vol. 9, 2018, doi: 10.3389/fmicb.2018.02151.

S. Aghamiri et al., “Targeting siRNA in colorectal cancer therapy: Nanotechnology comes into view,” J. Cell. Physiol., vol. 234, pp. 14818–14827, 2019, doi: 10.1002/jcp.28281.

S. Aghamiri et al., “siRNA nanotherapeutics: A promising strategy for anti-HBV therapy,” IET Nanobiotechnol., vol. 13, pp. 457–463, 2019, doi: 10.1049/iet-nbt.2018.5286.

R. Flisiak, J. Jaroszewicz, and M. Łucejko, “siRNA drug development against hepatitis B virus infection,” Expert Opin. Biol. Ther., vol. 18, pp. 609–617, 2018, doi: 10.1080/14712598.2018.1472231.

R. Bella et al., “Removal of HIV DNA by CRISPR from patient blood engrafts in humanised mice,” Mol. Ther. Nucleic Acids, vol. 12, pp. 275–282, 2018.

A. Carr, “Toxicity of antiretroviral therapy and implications for drug development,” Nat. Rev. Drug Discov., vol. 2, pp. 624–634, 2003.

H. K. Liao et al., “Use of the CRISPR/Cas9 system as an intracellular defence against HIV-1 infection in human cells,” Nat. Commun., vol. 6, 2015, Art. no. 6413, doi: 10.1038/ncomms7413.

R. Kaminski et al., “Elimination of HIV-1 genomes from human T-lymphoid cells by CRISPR/Cas9 gene editing,” Sci. Rep., vol. 6, 2016, Art. no. 22555, doi: 10.1038/srep22555.

R. Kaminski et al., “Excision of HIV-1 DNA by gene editing: A proof-of-concept in vivo study,” Gene Ther., vol. 23, pp. 690–695, 2016, doi: 10.1038/gt.2016.41.

C. Lee, “CRISPR/Cas9-based antiviral strategy: Current status and the potential challenge,” Molecules, vol. 24, 2019, Art. no. 1349, doi: 10.3390/molecules24071349.

P. Mohanraju et al., “Diverse evolutionary roots and mechanistic variations of the CRISPR-Cas systems,” Science, vol. 353, 2016.

P. D. Hsu, E. S. Lander, and F. Zhang, “Development and applications of CRISPR-Cas9 for genome engineering,” Cell, vol. 157, pp. 1262–1278, 2014.

S. H. Sternberg and J. A. Doudna, “Expanding the biologist toolkit with CRISPR-Cas9,” Mol. Cell, vol. 58, pp. 568–574, 2015.

J. A. Soppe and R. J. Lebbink, “Antiviral goes viral: Harnessing CRISPR/Cas9 to combat viruses in humans,” Trends Microbiol., vol. 25, pp. 833–850, 2017.

F. J. Mojica and F. Rodriguez-Valera, “The discovery of CRISPR in archaea and bacteria,” FEBS J., vol. 283, pp. 3162–3169, 2016, doi: 10.1111/febs.13766.

C. Escalona-Noguero, M. Lopez-Valls, and B. Sot, “CRISPR/Cas technology as a promising weapon to combat viral infections,” BioEssays, vol. 43, 2021, Art. no. e2000315, doi: 10.1002/bies.202000315.

J. Zhou et al., “One-step generation of different immunodeficient mice with multiple gene modifications by CRISPR/Cas9 mediated genome engineering,” Int. J. Biochem. Cell Biol., vol. 46, pp. 49–55, 2014, doi: 10.1016/j.biocel.2013.10.010.

G. Janusz et al., “Laccase properties, physiological functions, and evolution,” Int. J. Mol. Sci., vol. 21, 2020, Art. no. 966.

Y. Ishino, M. Krupovic, and P. Forterre, “History of CRISPR-Cas from encounter with a mysterious,” J. Bacteriol., vol. 200, 2018, Art. no. e00580-17.

N. Guo, J. B. Liu, W. Li, Y. S. Ma, and D. Fu, “The power and the promise of CRISPR/Cas9 genome editing for clinical application with gene therapy,” J. Adv. Res., vol. 40, pp. 135–152, 2021.

A. Karre, “Gene editing technology,” 2020. [Online]. Available: https://www.researchgate.net/publication/347442835_GENE_EDITING_TECHNOLOGY (accessed Nov. 10, 2022).

J. M. Crudele and J. S. Chamberlain, “Cas9 immunity creates challenges for CRISPR gene editing therapies,” Nat. Commun., vol. 9, 2018, Art. no. 3497.

L. Arora and A. Narula, “Gene editing and crop improvement using CRISPR-Cas9 system,” Front. Plant Sci., vol. 8, 2017, Art. no. 1932.

J. Kweon et al., “Engineered prime editors with PAM flexibility,” Mol. Ther., vol. 29, pp. 2001–2007, 2021.

F. A. Ran et al., “Genome engineering using the CRISPR-Cas9 system,” Nat. Protoc., vol. 8, pp. 2281–2308, 2013.

P. Bialk, N. Rivera-Torres, B. Strouse, and E. B. Kmiec, “Regulation of gene editing activity directed by single-stranded oligonucleotides and CRISPR/Cas9 systems,” PLoS ONE, vol. 10, 2015, Art. no. e0129308.

P. Horvath and R. Barrangou, “CRISPR/Cas, the immune system of bacteria and archaea,” Science, vol. 327, pp. 167–170, 2010.

K. S. Makarova et al., “Evolutionary classification of CRISPR–Cas systems: A burst of class 2 and derived variants,” Nat. Rev. Microbiol., vol. 18, pp. 67–83, 2020.

P. D. Hsu et al., “DNA targeting specificity of RNA-guided Cas9 nucleases,” Nat. Biotechnol., vol. 31, pp. 827–832, 2013, doi: 10.1038/nbt.2647.

A. E. Smith and A. Helenius, “How viruses enter animal cells,” Science, vol. 304, 2004, Art. no. 237, doi: 10.1126/science.1094823.

A. Nasir, E. Romero-Severson, and J.-M. Claverie, “Investigating the concept and origin of viruses,” Trends Microbiol., vol. 28, pp. 959–967, 2020, doi: 10.1016/j.tim.2020.08.003.

H. de Buhr and R. J. Lebbink, “Harnessing CRISPR to combat human viral infections,” Curr. Opin. Immunol., vol. 54, pp. 123–129, 2018, doi: 10.1016/j.coi.2018.06.002.

C. Escalona-Noguero, M. Lopez-Valls, and B. Sot, “CRISPR/Cas technology as a promising weapon to combat viral infections,” BioEssays, vol. 43, 2021, Art. no. 2000315, doi: 10.1002/bies.202000315.

C. M. Traylen et al., “Virus reactivation: A panoramic view in human infections,” Future Virol., vol. 6, pp. 451–463, 2011, doi: 10.2217/fvl.11.21.

Z. Nehme, S. Pasquereau, and G. Herbein, “Control of viral infections by epigenetic targeted therapy,” Clin. Epigenetics, vol. 11, 2019, Art. no. 55, doi: 10.1186/s13148-019-0654-9.

A. De Leo, A. Calderon, and P. M. Lieberman, “Control of viral latency by episome maintenance proteins,” Trends Microbiol., vol. 28, pp. 150–162, 2020, doi: 10.1016/j.tim.2019.09.002.

C. Fenwick et al., “T-cell exhaustion in HIV infection,” Immunol. Rev., vol. 292, pp. 149–163, 2019, doi: 10.1111/imr.12823.

S. Tsukuda and K. Watashi, “Hepatitis B virus biology and life cycle,” Antiviral Res., vol. 182, 2020, Art. no. 104925, doi: 10.1016/j.antiviral.2020.104925.

F. R. van Diemen et al., “CRISPR/Cas9-mediated genome editing of herpesviruses limits productive and latent infections,” PLoS Pathog., vol. 12, 2016, Art. no. e1005701, doi: 10.1371/journal.ppat.1005701.

J. L. Hsu and S. L. Glaser, “Epstein–Barr virus-associated malignancies: Epidemiologic patterns and etiologic implications,” Crit. Rev. Oncol. Hematol., vol. 34, pp. 27–53, 2000, doi: 10.1016/S1040-8428(00)00046-9.

E. M. Kennedy et al., “Inactivation of the human papillomavirus E6 or E7 gene in cervical carcinoma cells by using a bacterial CRISPR/Cas RNA-guided endonuclease,” J. Virol., vol. 88, pp. 11965–11972, 2014, doi: 10.1128/JVI.01879-14.

Y. Y. Chou et al., “Inhibition of JCPyV infection mediated by targeted viral genome editing using CRISPR/Cas9,” Sci. Rep., vol. 6, 2016, Art. no. 36921, doi: 10.1038/srep36921.

D. Cyranoski, “Chinese scientists to pioneer first human CRISPR trial,” Nature, vol. 535, pp. 476–477, 2016, doi: 10.1038/nature.2016.20302.

P. Hou et al., “Genome editing of CXCR4 by CRISPR/Cas9 confers cells resistance to HIV-1 infection,” Sci. Rep., vol. 5, 2015, Art. no. 15577, doi: 10.1038/srep15577.

M. R. O’Connell et al., “Programmable RNA recognition and cleavage by CRISPR/Cas9,” Nature, vol. 516, pp. 263–266, 2014, doi: 10.1038/nature13769.

V. N. Kim, “RNA-targeting CRISPR comes of age,” Nat. Biotechnol., vol. 36, pp. 44–45, 2018, doi: 10.1038/nbt.4054.

O. O. Abudayyeh et al., “RNA targeting with CRISPR–Cas13,” Nature, vol. 550, pp. 280–284, 2017, doi: 10.1038/nature24049.

T. M. Nguyen, Y. Zhang, and P. P. Pandolfi, “Virus against virus: A potential treatment for 2019-nCov (SARS-CoV-2) and other RNA viruses,” Cell Res., vol. 30, pp. 189–190, 2020, doi: 10.1038/s41422-020-0290-0.

F. Gao et al., “Origin of HIV-1 in the chimpanzee Pan troglodytes troglodytes,” Nature, vol. 397, pp. 436–441, 1999, doi: 10.1038/17130.

Joint United Nations Programme on HIV/AIDS (UNAIDS), “Fact sheet—latest global and regional statistics on the status of the HIV epidemic,” Geneva, Switzerland, 2019.

T. Lengauer and T. Sing, “Bioinformatics-assisted anti-HIV therapy,” Nat. Rev. Microbiol., vol. 4, pp. 790–797, 2006, doi: 10.1038/nrmicro1477.

H. F. Günthard et al., “Human immunodeficiency virus drug resistance: 2018 recommendations of the International Antiviral Society–USA panel,” Clin. Infect. Dis., vol. 68, pp. 177–187, 2019, doi: 10.1093/cid/ciy463.

L. Yin et al., “CRISPR/Cas9 inhibits multiple steps of HIV-1 infection,” Hum. Gene Ther., vol. 29, pp. 1264–1276, 2018, doi: 10.1089/hum.2018.018.

M. M. Lederman et al., “Biology of CCR5 and its role in HIV infection and treatment,” JAMA, vol. 296, pp. 815–826, 2006, doi: 10.1001/jama.296.7.815.

C. B. Wilen et al., “Engineering HIV-resistant human CD4+ T cells with CXCR4-specific zinc-finger nucleases,” PLoS Pathog., vol. 7, 2011, Art. no. e1002020, doi: 10.1371/journal.ppat.1002020.

G. Hütter et al., “Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation,” N. Engl. J. Med., vol. 360, pp. 692–698, 2009, doi: 10.1056/NEJMoa0802905.

Z. Liu et al., “Genome editing of the HIV co-receptors CCR5 and CXCR4 by CRISPR-Cas9 protects CD4(+) T cells from HIV-1 infection,” Retrovirology, vol. 7, 2017, Art. no. 47, doi: 10.1186/s13578-017-0174-2.

J. Ding and Y. Liu, “Knowledge from London and Berlin: Finding threads to a functional HIV cure,” Front. Immunol., vol. 12, 2021, doi: 10.3389/fimmu.2021.688747.

Y. Tagaya and R. C. Gallo, “The exceptional oncogenicity of HTLV-1,” Front. Microbiol., vol. 8, 2017, Art. no. 1425.

R. Grassmann, M. Aboud, and K.-T. Jeang, “Molecular mechanisms of cellular transformation by HTLV-1 Tax,” Oncogene, vol. 24, pp. 5976–5985, 2005.

J. Arnold et al., “Human T-cell leukaemia virus type-1 antisense-encoded gene, HBZ, promotes T-lymphocyte proliferation,” Blood, vol. 112, pp. 3788–3797, 2008.

S. A. Ghezeldasht et al., “HTLV-1 oncovirus-host interactions: From entry to the manifestation of associated diseases,” Rev. Med. Virol., 2021.

G. Wang, N. Zhao, B. Berkhout, and A. T. Das, “CRISPR-Cas based antiviral strategies against HIV-1,” Virus Res., vol. 244, pp. 321–332, 2018.

E. Kieff, “Epstein–Barr virus and its replication,” 2007, pp. 2603–2654. (incomplete publisher info as provided).

A. Komissarov et al., “Increase in sensitivity of HEK293FT cells to influenza infection by CRISPR-Cas9-mediated knockout of IRF7 transcription factor,” 2019, pp. 749–757. (incomplete source info as provided).

T. Kanda et al., “Highly efficient CRISPR/Cas9-mediated cloning and functional characterisation of gastric cancer-derived Epstein–Barr virus strains,” 2016, pp. 4383–4393. (incomplete source info as provided).

J. Wang and S. R. Quake, “RNA-guided endonuclease provides a therapeutic strategy to cure latent herpesviridae infection,” Proc. Natl. Acad. Sci. U.S.A., vol. 111, pp. 13157–13162, 2014, doi: 10.1073/pnas.1410785111.

F. R. van Diemen et al., “CRISPR/Cas9-mediated genome editing of herpesviruses limits productive and latent infections,” PLoS Pathog., vol. 12, 2016, Art. no. e1005701, doi: 10.1371/journal.ppat.1005701.

D. S. Hsu et al., “Targeting HPV16 DNA using CRISPR/Cas inhibits anal cancer growth in vivo,” 2018, pp. 475–482. (incomplete source info as provided).

Z. Hu et al., “Disruption of HPV16-E7 by the CRISPR/Cas system induces apoptosis and growth inhibition in HPV16-positive human cervical cancer cells,” 2014. (incomplete source info as provided).

E. M. Kennedy et al., “Inactivation of the human papillomavirus E6 or E7 gene in cervical carcinoma cells by using a bacterial CRISPR/Cas RNA-guided endonuclease,” J. Virol., vol. 88, pp. 11965–11972, 2014, doi: 10.1128/JVI.01879-14.

S. Zhen et al., “In vitro and in vivo synergistic therapeutic effect of cisplatin with human papillomavirus16 E6/E7 CRISPR/Cas9 on cervical cancer cell line,” Transl. Oncol., vol. 9, pp. 498–504, 2016, doi: 10.1016/j.tranon.2016.10.002.

M. Bakhrebah et al., “CRISPR technology: New paradigm to target the infectious disease pathogens,” 2018, pp. 3448–3452. (incomplete source info as provided).

G. Sharma et al., “CRISPR-Cas9: A preclinical and clinical perspective for the treatment of human diseases,” 2021, pp. 571–586. (incomplete source info as provided).

M. Saeed et al., “Efficient replication of genotype 3a and 4a hepatitis C virus replicons in human hepatoma cells,” 2012, pp. 5365–5373. (incomplete source info as provided).

M. U. Ashraf et al., “CRISPRCas13a-mediated targeting of hepatitis C virus internal-ribosomal entry site (IRES) as an effective antiviral strategy,” 2021, Art. no. 111239. (incomplete journal info as provided).

G. Neumann, T. Noda, and Y. Kawaoka, “Emergence and pandemic potential of swine-origin H1N1 influenza virus,” Nature, vol. 459, pp. 931–939, 2009.

C. F. Basler and P. V. Aguilar, “Progress in identifying virulence determinants of the 1918 H1N1 and the Southeast Asian H5N1 influenza A viruses,” 2008, pp. 166–178. (incomplete journal info as provided).

V. N. Petrova and C. A. Russell, “The evolution of seasonal influenza viruses,” Nat. Rev. Microbiol., vol. 16, pp. 47–60, 2018.

C. Li, Z. Bu, and H. Chen, “Avian influenza vaccines against H5N1 bird flu,” 2014, pp. 147–156. (incomplete journal info as provided).

G. Neumann et al., “H5N1 influenza viruses: Outbreaks and biological properties,” 2010, pp. 51–61. (incomplete journal info as provided).

C. Reed et al., “Characterising wild bird contact and seropositivity to highly pathogenic avian influenza A (H5N1) virus in Alaskan residents,” 2014, pp. 516–523. (incomplete journal info as provided).

A. Challagulla, K. A. Schat, and T. J. Doran, “In vitro inhibition of influenza virus using CRISPR/Cas13a in chicken cells,” 2021, p. 40. (incomplete journal info as provided).

A. Challagulla et al., “In vivo inhibition of Marek’s disease virus in transgenic chickens expressing Cas9 and gRNA against ICP4,” 2021, Art. no. 164. (incomplete journal info as provided).

C. Song et al., “Advances in delivery systems for CRISPR/Cas-mediated cancer treatment: A focus on viral vectors and extracellular vesicles,” Front. Immunol., vol. 15, 2024, Art. no. 1444437.

J. S. LaFountaine, K. Fathe, and H. D. C. Smyth, “Delivery and therapeutic applications of gene editing technologies, ZFNs, TALENs, and CRISPR/Cas9,” Int. J. Pharm., vol. 494, pp. 180–194, 2015.

H. Yin et al., “Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype,” Nat. Biotechnol., vol. 32, p. 952, 2014.

C. E. Nelson et al., “Long-term evaluation of AAV-CRISPR genome editing for Duchenne muscular dystrophy,” Nat. Med., vol. 25, pp. 427–432, 2019.

K. S. Hanlon et al., “High levels of AAV vector integration into CRISPR-induced DNA breaks,” Nat. Commun., vol. 10, pp. 1–11, 2019.

J. Kaiser, “Virus used in gene therapies may pose cancer risk, dog study hints,” Science, 2020, doi: 10.1126/science.aba7696.

C. L. Ventola, “The nanomedicine revolution: Part 1: Emerging concepts,” Pharm. Ther., vol. 37, no. 9, p. 512, 2012.

J. D. Sander and J. K. Joung, “CRISPR-Cas systems for editing, regulating and targeting genomes,” Nat. Biotechnol., vol. 32, no. 4, pp. 347–355, 2014.

A. Pickar-Oliver and C. A. Gersbach, “The next generation of CRISPR-Cas technologies and applications,” Nat. Rev. Mol. Cell Biol., vol. 20, no. 8, pp. 490–507, 2019.

D. Wilbie, J. Walther, and E. Mastrobattista, “Delivery aspects of CRISPR/Cas for in vivo genome editing,” Acc. Chem. Res., vol. 52, no. 6, pp. 1555–1564, 2019.

H. Yin, K. J. Kauffman, and D. G. Anderson, “Delivery technologies for genome editing,” Nat. Rev. Drug Discov., vol. 16, no. 6, pp. 387–399, 2017.

M. E. McClements and R. E. MacLaren, “Adeno-associated virus (AAV) dual vector strategies for gene therapy encoding large transgenes,” Yale J. Biol. Med., vol. 90, no. 4, pp. 611–623, 2017.

K. Chamberlain, J. M. Riyad, and T. Weber, “Expressing transgenes that exceed the packaging capacity of adeno-associated virus capsids,” Hum. Gene Ther. Methods, vol. 27, no. 1, pp. 1–12, 2016.

M. Teng, Y. Yao, V. Nair, and J. Luo, “Latest advances of virology research using CRISPR/Cas9-based gene-editing technology and its application to vaccine development,” Viruses, vol. 13, no. 5, Art. no. 779, 2021.

H. Naeem et al., “CRISPR/Cas system toward the development of next-generation recombinant vaccines: Current scenario and future prospects,” Arab. J. Sci. Eng., vol. 48, pp. 826–837, 2022.

X. Hou, T. Zaks, R. Langer, and Y. Dong, “Lipid nanoparticles for mRNA delivery,” Nat. Rev. Mater., vol. 6, pp. 1078–1094, 2021.

E. Rohner et al., “Unlocking the promise of mRNA therapeutics,” Nat. Biotechnol., vol. 40, pp. 1586–1600, 2022.

Y. Eygeris, M. Gupta, J. Kim, and G. Sahay, “Chemistry of lipid nanoparticles for RNA delivery,” Acc. Chem. Res., vol. 55, pp. 2–12, 2022.

M. Francia et al., “The biomolecular corona of lipid nanoparticles for gene therapy,” Bioconjugate Chem., vol. 31, no. 9, pp. 2046–2059, 2020.

S. W. Wang et al., “Current applications and future perspective of CRISPR/Cas9 gene editing in cancer,” Mol. Cancer, vol. 21, Art. no. 57, 2022.

J. Luo et al., “Adeno-associated virus-mediated cancer gene therapy: Current status,” Cancer Lett., vol. 356, pp. 347–356, 2015.

C. Li and R. J. Samulski, “Engineering adeno-associated virus vectors for gene therapy,” Nat. Rev. Genet., vol. 21, pp. 255–272, 2020.

C. E. Nelson and C. A. Gersbach, “Engineering delivery vehicles for genome editing,” Annu. Rev. Chem. Biomol. Eng., vol. 7, pp. 637–662, 2016.

K. Lundstrom, “Viral vectors in gene therapy,” Diseases, vol. 6, Art. no. 42, 2018.

D. A. Kuzmin et al., “The clinical landscape for AAV gene therapies,” Nat. Rev. Drug Discov., vol. 20, pp. 173–174, 2021.

T. Burdett and S. Nuseibeh, “Changing trends in the development of AAV-based gene therapies: A meta-analysis of past and present therapies,” Gene Ther., vol. 30, pp. 323–335, 2023.

D. Wang, F. Zhang, and G. Gao, “CRISPR-based therapeutic genome editing: Strategies and in vivo delivery by AAV vectors,” Cell, vol. 181, pp. 136–150, 2020.

R. Waehler, S. J. Russell, and D. T. Curiel, “Engineering targeted viral vectors for gene therapy,” Nat. Rev. Genet., vol. 8, no. 8, pp. 573–587, 2007.

J. Reetz, O. Herchenroder, and B. M. Putzer, “Peptide-based technologies to alter adenoviral vector tropism: Ways and means for systemic treatment of cancer,” Viruses, vol. 6, no. 4, pp. 1540–1563, 2014.

H. Takemoto, K. Miyata, N. Nishiyama, and K. Kataoka, “Bioresponsive polymer-based nucleic acid carriers,” Adv. Genet., vol. 88, pp. 289–323, 2014.

A. C. Komor, Y. B. Kim, M. S. Packer, J. A. Zuris, and D. R. Liu, “Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage,” Nature, vol. 533, no. 7603, pp. 420–424, 2016, doi: 10.1038/nature17946.

N. M. Gaudelli et al., “Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage,” Nature, vol. 551, no. 7681, pp. 464–471, 2017, doi: 10.1038/nature24644.

M. Jinek et al., “A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity,” Science, vol. 337, no. 6096, pp. 816–821, 2012, doi: 10.1126/science.1225829.

R. Shegokar and R. H. Müller, “Nanocrystals: Industrially feasible multifunctional formulation technology for poorly soluble actives,” Int. J. Pharm., vol. 399, pp. 129–139, 2010.

S. B. Lim, A. Banerjee, and H. Önyüksel, “Improvement of drug safety by the use of lipid-based nanocarriers,” J. Control. Release, vol. 163, pp. 34–45, 2012.