CRISPR-Cas9 gene editing technology in human gene therapy: the new realm of medicine

Authors

  • Manasa M. S. Cambridge University Hospitals, Cambridge, United Kingdom

DOI:

https://doi.org/10.18203/2349-3933.ijam20220796

Keywords:

CRISPR-Cas9, Gene therapy, Gene editing, LHNPs

Abstract

Gene therapy has a huge clinical relevance in the present therapeutic world and is one of the many research fields of biology which received many benefits from the recent advancements of modern clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 gene editing technology. Researchers are on the way to make significant changes in the ways of treating genetic abnormalities. An increase in the number of approved clinical trials of CRISPR based gene therapy shows we are not too far from eliminating deadly diseases such as acquired immunodeficiency syndrome (AIDS), cancer and many inherited genetic conditions from the society. However, there are some challenges associated with the development of CRISPR technology in medical field most of which revolves around its safety, efficiency and ethics. Lack of an optimized method by which the CRISPR-Cas9 expression cassette can be delivered to cells is one of the main challenges when it comes to its application in human gene therapy. Although viral vectors are the most common delivery systems used in gene therapy, recent researches show promising results on using lipid- based l delivery systems such as liposome-templated hydrogel nanoparticles (LHNPs). As these could eliminate the safety concerns of using viral vectors, it is expected to have potential therapeutic applications in future. Nevertheless, the efficiency of non-viral systems is still not fully comparable with that of viral vectors. Hence, CRISPR based therapies might take longer than expected to be prevalent in the medical field. In this short review, the recent advances of CRISPR technology in gene therapy is discussed along with its challenges and limitations.

Author Biography

Manasa M. S., Cambridge University Hospitals, Cambridge, United Kingdom

India

References

Uddin F, Rudin CM, Sen T. CRISPR Gene Therapy: Applications, Limitations, and Implications for the Future. Front Oncol. 2020;10:1387.

Zhu H, Li C, Gao C. Applications of CRISPR-Cas in agriculture and plant biotechnology. Nat Rev Mol Cell Biol. 2020;21(11):661-77.

Schmidt F, Platt RJ. Applications of CRISPR-Cas for synthetic biology and genetic recording. Curr Opin Systems Biol. 2011;5:9-15.

Xie Y, Yang Y, He Y, Wang X, Zhang P, Li H, Liang S. Synthetic Biology Speeds Up Drug Target Discovery. Front Pharmacol. 2020;11:119.

Ishino Y, Krupovic M, Forterre P. History of CRISPR-Cas from encounter with a mysterious repeated sequence to genome editing technology. J Bacteriol. 2018;200(7):e00580-17.

Makarova KS, Grishin NV, Shabalina SA, Wolf YI, Koonin EV. A putative RNA-interference-based immune system in prokaryotes: computational analysis of the predicted enzymatic machinery, functional analogies with eukaryotic RNAi, and hypothetical mechanisms of action. Biology Direct. 2006;1(1):1-26.

Shah SA, Erdmann S, Mojica FJ, Garrett RA. Protospacer recognition motifs: mixed identities and functional diversity. RNA Biology. 2013;10(5):891-9.

Fridovich-Keil JL. "Gene editing". Encyclopedia Britannica. 2019. Available at: https://www. britannica.com/science/gene-editing. Accessed on 27 October 2021.

Ledford H, Callaway E. Pioneers of CRISPR gene editing win Chemistry nobel. Nature. 2020;586(7829):346-7.

Gaj T, Sirk SJ, Shui SL, Liu J. Genome-editing technologies: principles and applications. Cold Spring Harbor perspectives in biology. 2016;8(12):a023754.

Li H, Yang Y, Hong W, Huang M, Wu M, Zhao X. Applications of genome editing technology in the targeted therapy of human diseases: mechanisms, advances and prospects. Signal transduction and targeted therapy. 2020;5(1):1-23.

Gupta RM, Musunuru K. Expanding the genetic editing tool kit: ZFNs, TALENs, and CRISPR-Cas9. J Clin Investig. 2014;124(10):4154-61.

Mitha F. The Return of Gene Therapy. [online] Labiotech.eu. 2019. Available at: https://www. labiotech.eu/in-depth/gene-therapy-history/. Accessed on 27 October 2021.

Wirth T, Parker N, Ylä-Herttuala S. History of gene therapy. Gene. 2013;525(2):162-9.

Gene therapy needs a long-term approach. Nature Medicine. 2021;27(4):563.

Belete TM. The Current Status of Gene Therapy for the Treatment of Cancer. Biologics: Targets & Therapy. 2021;15:67.

Ginn SL, Amaya AK, Alexander IE, Edelstein M, Abedi MR. Gene therapy clinical trials worldwide to 2017: An update. J Gene Med. 2018;20(5):e3015.

Cockroft A, Wilson A. Comparability: what we can learn from the review of advanced therapy medicinal products. Regenerative Medicine. 2021;16(07):655-67.

FDA Approves First Cell-Based Gene Therapy for Adult Patients with Multiple Myeloma. FDA. 2021. Available at: https://www.fda.gov/news-events/ press-announcements/fda-approves-first-cell-based-gene-therapy-adult-patients-multiple-myeloma. Accessed on 27 October 2021.

Szebik I, Glass KC. Ethical issues of human germ-cell therapy: a preparation for public discussion. Academic Medicine. 2001;76(1):32-8.

Brunn C. Challenges and opportunities in gene therapy development. 2021. Available at: https://www.drugtargetreview.com/article/92596/challenges-and-opportunities-in-gene-therapy-development/. Accessed on 27 October 2021.

Coopman K, Medcalf N. From production to patient: challenges and approaches for delivering cell therapies. StemBook. 2014.

Cooper E. Five-month old baby becomes first patient to receive world’s most expensive drug. Pharmafield. 2021. Available at: https://pharmafield.co.uk/ pharma_news/five-month-old-baby-becomes-first-patient-to-receive-worlds-most-expensive-drug/. Accessed on 27 October 2021.

Zhen S, Li X. Liposomal delivery of CRISPR/Cas9. Cancer gene therapy. 2020;27(7):515-27.

Li L, Hu S, Chen X. Non-viral delivery systems for CRISPR/Cas9-based genome editing: Challenges and opportunities. Biomaterials. 2018;171:207-18.

Chen Z, Liu F, Chen Y, Liu J, Wang X, Chen AT, et al. Targeted delivery of CRISPR/Cas9‐mediated cancer gene therapy via liposome‐templated hydrogel nanoparticles. Advanced functional materials. 2017;27(46):1703036.

Aksoy YA, Yang B, Chen W, Hung T, Kuchel RP, Zammit NW, et al. Spatial and Temporal control of CRISPR-Cas9-mediated gene editing delivered via a light-triggered liposome system. ACS Applied Materials & Interfaces. 2020;12(47):52433-44.

Yip BH. Recent advances in CRISPR/Cas9 delivery strategies. Biomolecules. 2020;10(6):839.

Behr M, Zhou J, Xu B, Zhang H. In vivo delivery of CRISPR-Cas9 therapeutics: Progress and challenges. Acta Pharm Sin B. 2021;11(8):2150-71.

Intellia and Regeneron Announce Landmark Clinical Data Showing Deep Reduction in Disease-Causing Protein After Single Infusion of NTLA-2001, an Investigational CRISPR Therapy for Transthyretin (ATTR) Amyloidosis. Intellia Therapeutics. 2021. Available at: https://ir.intelliatx.com/news-releases/ news-release-details/intellia-and-regeneron-announce-landmark-clinical-data-showing. Accessed on 23 October 2021.

Cyranoski D. Chinese scientists to pioneer first human CRISPR trial. Nature News. 2016;535(7613):476.

FDA approves first test of CRISPR to correct genetic defect causing sickle cell disease. [online] Berkeley News. 2019. Available at: https://news.berkeley. edu/2021/03/30/fda-approves-first-test-of-crispr-to-correct-genetic-defect-causing-sickle-cell-disease/. Accessed on 23 October 2021.

Sheridan C. Go-ahead for first in-body CRISPR medicine testing. Nature Biotechnology. 2018;36:907-8.

Philippidis A. Editas Early Data for CRISPR Therapy EDIT-101 Shows Efficacy “Signals” in Two Patients. [online] GEN - Genetic Engineering and Biotechnology News. 2021. Available at: https://www.genengnews.com/news/editas-early-data-for-crispr-therapy-edit-101-shows-efficacy-signals-in-two-patients. Accessed on 27 October 2021.

Find Trials. Available at: https://clinicaltrials.gov/. Accessed on 27 October 2021.

Antoniou P, Miccio A, Brusson M. Base and prime editing technologies for blood disorders. Frontiers in Genome Editing. 2021;3:1.

Cyranoski D. The CRISPR-baby scandal: what's next for human gene-editing. Nature. 2019;566(7745):440-3.

Downloads

Published

2022-03-24

Issue

Section

Review Articles