Biomaterials-mediated CRISPR/Cas9 Delivery: Recent Challenges and Opportunities in Gene Therapy

Overview

Journal Front Chem

Specialty Chemistry

Date 2023 Oct 16

PMID 37841202

Authors

Ankit Kumar Dubey

Ebrahim Mostafavi

Affiliations

Soon will be listed here.

Abstract

The use of biomaterials in delivering CRISPR/Cas9 for gene therapy in infectious diseases holds tremendous potential. This innovative approach combines the advantages of CRISPR/Cas9 with the protective properties of biomaterials, enabling accurate and efficient gene editing while enhancing safety. Biomaterials play a vital role in shielding CRISPR/Cas9 components, such as lipid nanoparticles or viral vectors, from immunological processes and degradation, extending their effectiveness. By utilizing the flexibility of biomaterials, tailored systems can be designed to address specific genetic diseases, paving the way for personalized therapeutics. Furthermore, this delivery method offers promising avenues in combating viral illnesses by precisely modifying pathogen genomes, and reducing their pathogenicity. Biomaterials facilitate site-specific gene modifications, ensuring effective delivery to infected cells while minimizing off-target effects. However, challenges remain, including optimizing delivery efficiency, reducing off-target effects, ensuring long-term safety, and establishing scalable production techniques. Thorough research, pre-clinical investigations, and rigorous safety evaluations are imperative for successful translation from the laboratory to clinical applications. In this review, we discussed how CRISPR/Cas9 delivery using biomaterials revolutionizes gene therapy and infectious disease treatment, offering precise and safe editing capabilities with the potential to significantly improve human health and quality of life.

Citing Articles

Pharmacomicrobiomics: a new field contributing to optimizing drug therapy in Parkinson's disease.

Zhang Y, Mo C, Ai P, He X, Xiao Q, Yang X Gut Microbes. 2025; 17(1):2454937.

PMID: 39875349 PMC: 11776486. DOI: 10.1080/19490976.2025.2454937.

Systematic Review of Vaccine Strategies Against Tritrichomonas foetus Infection in Cattle: Insights, Challenges, and Prospects.

Santos J, Boe-Hansen G, Siddle H, Nguyen L, Raza A, McGowan M Parasite Immunol. 2025; 47(1):e70003.

PMID: 39838701 PMC: 11751591. DOI: 10.1111/pim.70003.

Nanoparticle Strategies for Treating CNS Disorders: A Comprehensive Review of Drug Delivery and Theranostic Applications.

Toader C, Dumitru A, Eva L, Serban M, Covache-Busuioc R, Ciurea A Int J Mol Sci. 2025; 25(24.

PMID: 39769066 PMC: 11676454. DOI: 10.3390/ijms252413302.

Unlocking the Potential of Silver Nanoparticles: From Synthesis to Versatile Bio-Applications.

Almatroudi A Pharmaceutics. 2024; 16(9).

PMID: 39339268 PMC: 11435049. DOI: 10.3390/pharmaceutics16091232.

Natural Food Components as Biocompatible Carriers: A Novel Approach to Glioblastoma Drug Delivery.

Tharamelveliyil Rajendran A, Vadakkepushpakath A Foods. 2024; 13(17).

PMID: 39272576 PMC: 11394703. DOI: 10.3390/foods13172812.

References

Liu W, Li L, Jiang J, Wu M, Lin P . Applications and challenges of CRISPR-Cas gene-editing to disease treatment in clinics. Precis Clin Med. 2021; 4(3):179-191. PMC: 8444435. DOI: 10.1093/pcmedi/pbab014. View

Chan B, Leong K . Scaffolding in tissue engineering: general approaches and tissue-specific considerations. Eur Spine J. 2008; 17 Suppl 4:467-79. PMC: 2587658. DOI: 10.1007/s00586-008-0745-3. View

Lee S . Bacterial polyhydroxyalkanoates. Biotechnol Bioeng. 1996; 49(1):1-14. DOI: 10.1002/(SICI)1097-0290(19960105)49:1<1::AID-BIT1>3.0.CO;2-P. View

Mehta S, He T, Bajpayee A . Recent advances in targeted drug delivery for treatment of osteoarthritis. Curr Opin Rheumatol. 2020; 33(1):94-109. PMC: 8101446. DOI: 10.1097/BOR.0000000000000761. View

Clement F, Grockowiak E, Zylbersztejn F, Fossard G, Gobert S, Maguer-Satta V . Stem cell manipulation, gene therapy and the risk of cancer stem cell emergence. Stem Cell Investig. 2017; 4:67. PMC: 5539392. DOI: 10.21037/sci.2017.07.03. View

Ding Q, Strong A, Patel K, Ng S, Gosis B, Regan S . Permanent alteration of PCSK9 with in vivo CRISPR-Cas9 genome editing. Circ Res. 2014; 115(5):488-92. PMC: 4134749. DOI: 10.1161/CIRCRESAHA.115.304351. View

Cai L, Fisher A, Huang H, Xie Z . CRISPR-mediated genome editing and human diseases. Genes Dis. 2018; 3(4):244-251. PMC: 6150104. DOI: 10.1016/j.gendis.2016.07.003. View

Muringayil Joseph T, Mahapatra D, Esmaeili A, Piszczyk L, Hasanin M, Kattali M . Nanoparticles: Taking a Unique Position in Medicine. Nanomaterials (Basel). 2023; 13(3). PMC: 9920911. DOI: 10.3390/nano13030574. View

Ghadi A, Mahjoub S, Tabandeh F, Talebnia F . Synthesis and optimization of chitosan nanoparticles: Potential applications in nanomedicine and biomedical engineering. Caspian J Intern Med. 2014; 5(3):156-61. PMC: 4143737. View

10.

Herdiana Y, Wathoni N, Shamsuddin S, Muchtaridi M . Drug release study of the chitosan-based nanoparticles. Heliyon. 2022; 8(1):e08674. PMC: 8741465. DOI: 10.1016/j.heliyon.2021.e08674. View

11.

Liu F, Su H, Li M, Xie W, Yan Y, Shuai Q . Zwitterionic Modification of Polyethyleneimine for Efficient siRNA Delivery. Int J Mol Sci. 2022; 23(9). PMC: 9100541. DOI: 10.3390/ijms23095014. View

12.

Ma P, Mumper R . Paclitaxel Nano-Delivery Systems: A Comprehensive Review. J Nanomed Nanotechnol. 2013; 4(2):1000164. PMC: 3806207. DOI: 10.4172/2157-7439.1000164. View

13.

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

14.

Pan X, Veroniaina H, Su N, Sha K, Jiang F, Wu Z . Applications and developments of gene therapy drug delivery systems for genetic diseases. Asian J Pharm Sci. 2022; 16(6):687-703. PMC: 8737406. DOI: 10.1016/j.ajps.2021.05.003. View

15.

Huang G, Liu Y, Chen L . Chitosan and its derivatives as vehicles for drug delivery. Drug Deliv. 2017; 24(sup1):108-113. PMC: 8812576. DOI: 10.1080/10717544.2017.1399305. View

16.

Chen G, Abdeen A, Wang Y, Shahi P, Robertson S, Xie R . A biodegradable nanocapsule delivers a Cas9 ribonucleoprotein complex for in vivo genome editing. Nat Nanotechnol. 2019; 14(10):974-980. PMC: 6778035. DOI: 10.1038/s41565-019-0539-2. View

17.

Gopal S, Rodrigues A, Dordick J . Exploiting CRISPR Cas9 in Three-Dimensional Stem Cell Cultures to Model Disease. Front Bioeng Biotechnol. 2020; 8:692. PMC: 7326781. DOI: 10.3389/fbioe.2020.00692. View

18.

Liu S, Narancic T, Davis C, OConnor K . CRISPR-Cas9 Editing of the Synthesis of Biodegradable Polyesters Polyhydroxyalkanaotes (PHA) in Pseudomonas putida KT2440. Methods Mol Biol. 2021; 2397:341-358. DOI: 10.1007/978-1-0716-1826-4_17. View

19.

Dumas M, Xia S, Bear C, Ratjen F . Perspectives on the translation of in-vitro studies to precision medicine in Cystic Fibrosis. EBioMedicine. 2021; 73:103660. PMC: 8577330. DOI: 10.1016/j.ebiom.2021.103660. View

20.

Zhao Z, Li Y, Xie M . Silk fibroin-based nanoparticles for drug delivery. Int J Mol Sci. 2015; 16(3):4880-903. PMC: 4394455. DOI: 10.3390/ijms16034880. View