Non-Viral Delivery of CRISPR/Cas Cargo to the Retina Using Nanoparticles: Current Possibilities, Challenges, and Limitations

Overview

Journal Pharmaceutics

Publisher MDPI

Date 2022 Sep 23

PMID 36145593

Authors

Ahmed Salman

Ariel Kantor

Michelle E McClements

Gemma Marfany

Sonia Trigueros

Robert E MacLaren

Affiliations

Soon will be listed here.

Abstract

The discovery of the CRISPR/Cas system and its development into a powerful genome engineering tool have revolutionized the field of molecular biology and generated excitement for its potential to treat a wide range of human diseases. As a gene therapy target, the retina offers many advantages over other tissues because of its surgical accessibility and relative immunity privilege due to its blood-retinal barrier. These features explain the large advances made in ocular gene therapy over the past decade, including the first in vivo clinical trial using CRISPR gene-editing reagents. Although viral vector-mediated therapeutic approaches have been successful, they have several shortcomings, including packaging constraints, pre-existing anti-capsid immunity and vector-induced immunogenicity, therapeutic potency and persistence, and potential genotoxicity. The use of nanomaterials in the delivery of therapeutic agents has revolutionized the way genetic materials are delivered to cells, tissues, and organs, and presents an appealing alternative to bypass the limitations of viral delivery systems. In this review, we explore the potential use of non-viral vectors as tools for gene therapy, exploring the latest advancements in nanotechnology in medicine and focusing on the nanoparticle-mediated delivery of CRIPSR genetic cargo to the retina.

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References

Li Z, Zhang Y, Feng N . Mesoporous silica nanoparticles: synthesis, classification, drug loading, pharmacokinetics, biocompatibility, and application in drug delivery. Expert Opin Drug Deliv. 2019; 16(3):219-237. DOI: 10.1080/17425247.2019.1575806. View

Sundaram V, Moore A, Ali R, Bainbridge J . Retinal dystrophies and gene therapy. Eur J Pediatr. 2011; 171(5):757-65. DOI: 10.1007/s00431-011-1615-2. View

Stieger K, Lorenz B . Gene therapy for vision loss -- recent developments. Discov Med. 2010; 10(54):425-33. View

Alyautdin R, Khalin I, Nafeeza M, Haron M, Kuznetsov D . Nanoscale drug delivery systems and the blood-brain barrier. Int J Nanomedicine. 2014; 9:795-811. PMC: 3926460. DOI: 10.2147/IJN.S52236. View

Cideciyan A, Jacobson S, Beltran W, Sumaroka A, Swider M, Iwabe S . Human retinal gene therapy for Leber congenital amaurosis shows advancing retinal degeneration despite enduring visual improvement. Proc Natl Acad Sci U S A. 2013; 110(6):E517-25. PMC: 3568385. DOI: 10.1073/pnas.1218933110. View

Yeagle P . Modulation of membrane function by cholesterol. Biochimie. 1991; 73(10):1303-10. DOI: 10.1016/0300-9084(91)90093-g. View

Mitchell M, Billingsley M, Haley R, Wechsler M, Peppas N, Langer R . Engineering precision nanoparticles for drug delivery. Nat Rev Drug Discov. 2020; 20(2):101-124. PMC: 7717100. DOI: 10.1038/s41573-020-0090-8. View

Iyama T, Wilson 3rd D . DNA repair mechanisms in dividing and non-dividing cells. DNA Repair (Amst). 2013; 12(8):620-36. PMC: 3720834. DOI: 10.1016/j.dnarep.2013.04.015. View

Giannaccini M, Giannini M, Calatayud M, Goya G, Cuschieri A, Dente L . Magnetic nanoparticles as intraocular drug delivery system to target retinal pigmented epithelium (RPE). Int J Mol Sci. 2014; 15(1):1590-605. PMC: 3907888. DOI: 10.3390/ijms15011590. View

10.

Hamilton J, Tsuchida C, Nguyen D, Shy B, McGarrigle E, Sandoval Espinoza C . Targeted delivery of CRISPR-Cas9 and transgenes enables complex immune cell engineering. Cell Rep. 2021; 35(9):109207. PMC: 8236216. DOI: 10.1016/j.celrep.2021.109207. View

11.

Oh E, Park K, Choi J, Joo C, Hahn S . Synthesis, characterization, and preliminary assessment of anti-Flt1 peptide-hyaluronate conjugate for the treatment of corneal neovascularization. Biomaterials. 2009; 30(30):6026-34. DOI: 10.1016/j.biomaterials.2009.07.024. View

12.

Maeder M, Stefanidakis M, Wilson C, Baral R, Barrera L, Bounoutas G . Development of a gene-editing approach to restore vision loss in Leber congenital amaurosis type 10. Nat Med. 2019; 25(2):229-233. DOI: 10.1038/s41591-018-0327-9. View

13.

Liu Q, Wang C, Zheng Y, Zhao Y, Wang Y, Hao J . Virus-like nanoparticle as a co-delivery system to enhance efficacy of CRISPR/Cas9-based cancer immunotherapy. Biomaterials. 2020; 258:120275. DOI: 10.1016/j.biomaterials.2020.120275. View

14.

Burke P, Klumb L, Herberger J, Nguyen X, Harrell R, Zordich M . Poly(lactide-co-glycolide) microsphere formulations of darbepoetin alfa: spray drying is an alternative to encapsulation by spray-freeze drying. Pharm Res. 2004; 21(3):500-6. DOI: 10.1023/B:PHAM.0000019305.79599.a5. View

15.

Barrangou R, Horvath P . A decade of discovery: CRISPR functions and applications. Nat Microbiol. 2017; 2:17092. DOI: 10.1038/nmicrobiol.2017.92. View

16.

Nickerson J, Getz S, Sellers J, Chrenek M, Goodman P, Bernal C . DNA delivery in adult mouse eyes: an update with corneal outcomes. Methods Mol Biol. 2014; 1121:165-77. PMC: 4083748. DOI: 10.1007/978-1-4614-9632-8_15. View

17.

Flannery J, Zolotukhin S, Vaquero M, LaVail M, Muzyczka N, Hauswirth W . Efficient photoreceptor-targeted gene expression in vivo by recombinant adeno-associated virus. Proc Natl Acad Sci U S A. 1997; 94(13):6916-21. PMC: 21259. DOI: 10.1073/pnas.94.13.6916. View

18.

Collins F, Varmus H . A new initiative on precision medicine. N Engl J Med. 2015; 372(9):793-5. PMC: 5101938. DOI: 10.1056/NEJMp1500523. View

19.

Song F, Stieger K . Optimizing the DNA Donor Template for Homology-Directed Repair of Double-Strand Breaks. Mol Ther Nucleic Acids. 2017; 7:53-60. PMC: 5363683. DOI: 10.1016/j.omtn.2017.02.006. View

20.

Komor A, Kim Y, Packer M, Zuris J, Liu D . Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature. 2016; 533(7603):420-4. PMC: 4873371. DOI: 10.1038/nature17946. View