Non-viral Delivery Systems for CRISPR/Cas9-based Genome Editing: Challenges and Opportunities

Overview

Journal Biomaterials

Specialty Biomedical Engineering

Date 2018 Apr 29

PMID 29704747

Citations 150

Authors

Ling Li

Shuo Hu

Xiaoyuan Chen

Affiliations

Soon will be listed here.

Abstract

In recent years, CRISPR (clustered regularly interspaced short palindromic repeat)/Cas (CRISPR-associated) genome editing systems have become one of the most robust platforms in basic biomedical research and therapeutic applications. To date, efficient in vivo delivery of the CRISPR/Cas9 system to the targeted cells remains a challenge. Although viral vectors have been widely used in the delivery of the CRISPR/Cas9 system in vitro and in vivo, their fundamental shortcomings, such as the risk of carcinogenesis, limited insertion size, immune responses and difficulty in large-scale production, severely limit their further applications. Alternative non-viral delivery systems for CRISPR/Cas9 are urgently needed. With the rapid development of non-viral vectors, lipid- or polymer-based nanocarriers have shown great potential for CRISPR/Cas9 delivery. In this review, we analyze the pros and cons of delivering CRISPR/Cas9 systems in the form of plasmid, mRNA, or protein and then discuss the limitations and challenges of CRISPR/Cas9-based genome editing. Furthermore, current non-viral vectors that have been applied for CRISPR/Cas9 delivery in vitro and in vivo are outlined in details. Finally, critical obstacles for non-viral delivery of CRISPR/Cas9 system are highlighted and promising strategies to overcome these barriers are proposed.

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References

Haque M, Jeong J, Byun Y . Combination strategy of multi-layered surface camouflage using hyperbranched polyethylene glycol and immunosuppressive drugs for the prevention of immune reactions against transplanted porcine islets. Biomaterials. 2016; 84:144-156. DOI: 10.1016/j.biomaterials.2016.01.039. View

Hwang W, Fu Y, Reyon D, Maeder M, Tsai S, Sander J . Efficient genome editing in zebrafish using a CRISPR-Cas system. Nat Biotechnol. 2013; 31(3):227-9. PMC: 3686313. DOI: 10.1038/nbt.2501. View

Barrangou R, Doudna J . Applications of CRISPR technologies in research and beyond. Nat Biotechnol. 2016; 34(9):933-941. DOI: 10.1038/nbt.3659. View

Cho Y, Kim J, Park K . Polycation gene delivery systems: escape from endosomes to cytosol. J Pharm Pharmacol. 2003; 55(6):721-34. DOI: 10.1211/002235703765951311. View

Peer D, Karp J, Hong S, Farokhzad O, Margalit R, Langer R . Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol. 2008; 2(12):751-60. DOI: 10.1038/nnano.2007.387. View

Wu Y, Zhou H, Fan X, Zhang Y, Zhang M, Wang Y . Correction of a genetic disease by CRISPR-Cas9-mediated gene editing in mouse spermatogonial stem cells. Cell Res. 2014; 25(1):67-79. PMC: 4650588. DOI: 10.1038/cr.2014.160. View

Dawson M, Kouzarides T . Cancer epigenetics: from mechanism to therapy. Cell. 2012; 150(1):12-27. DOI: 10.1016/j.cell.2012.06.013. View

Hughes T, Langer S, Virtanen S, Chavez R, Watkins L, Milligan E . Immunogenicity of intrathecal plasmid gene delivery: cytokine release and effects on transgene expression. J Gene Med. 2009; 11(9):782-90. PMC: 3649870. DOI: 10.1002/jgm.1364. View

Prakash V, Moore M, Yanez-Munoz R . Current Progress in Therapeutic Gene Editing for Monogenic Diseases. Mol Ther. 2016; 24(3):465-74. PMC: 4786935. DOI: 10.1038/mt.2016.5. View

10.

Kleinstiver B, Pattanayak V, Prew M, Tsai S, Nguyen N, Zheng Z . High-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects. Nature. 2016; 529(7587):490-5. PMC: 4851738. DOI: 10.1038/nature16526. View

11.

Hou Z, Zhang Y, Propson N, Howden S, Chu L, Sontheimer E . Efficient genome engineering in human pluripotent stem cells using Cas9 from Neisseria meningitidis. Proc Natl Acad Sci U S A. 2013; 110(39):15644-9. PMC: 3785731. DOI: 10.1073/pnas.1313587110. View

12.

Ye L, Wang J, Tan Y, Beyer A, Xie F, Muench M . Genome editing using CRISPR-Cas9 to create the HPFH genotype in HSPCs: An approach for treating sickle cell disease and β-thalassemia. Proc Natl Acad Sci U S A. 2016; 113(38):10661-5. PMC: 5035856. DOI: 10.1073/pnas.1612075113. View

13.

Egger G, Liang G, Aparicio A, Jones P . Epigenetics in human disease and prospects for epigenetic therapy. Nature. 2004; 429(6990):457-63. DOI: 10.1038/nature02625. View

14.

Ran F, Cong L, Yan W, Scott D, Gootenberg J, Kriz A . In vivo genome editing using Staphylococcus aureus Cas9. Nature. 2015; 520(7546):186-91. PMC: 4393360. DOI: 10.1038/nature14299. View

15.

Wang Z, Zang C, Rosenfeld J, Schones D, Barski A, Cuddapah S . Combinatorial patterns of histone acetylations and methylations in the human genome. Nat Genet. 2008; 40(7):897-903. PMC: 2769248. DOI: 10.1038/ng.154. View

16.

Li Y, Wang H, Wang K, Hu Q, Yao Q, Shen Y . Targeted Co-delivery of PTX and TR3 siRNA by PTP Peptide Modified Dendrimer for the Treatment of Pancreatic Cancer. Small. 2016; 13(2). DOI: 10.1002/smll.201602697. View

17.

Zhou Y, Zhu S, Cai C, Yuan P, Li C, Huang Y . High-throughput screening of a CRISPR/Cas9 library for functional genomics in human cells. Nature. 2014; 509(7501):487-91. DOI: 10.1038/nature13166. View

18.

Xue W, Chen S, Yin H, Tammela T, Papagiannakopoulos T, Joshi N . CRISPR-mediated direct mutation of cancer genes in the mouse liver. Nature. 2014; 514(7522):380-4. PMC: 4199937. DOI: 10.1038/nature13589. View

19.

Bushby K, Finkel R, Birnkrant D, Case L, Clemens P, Cripe L . Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol. 2009; 9(1):77-93. DOI: 10.1016/S1474-4422(09)70271-6. View

20.

He C, Lu K, Liu D, Lin W . Nanoscale metal-organic frameworks for the co-delivery of cisplatin and pooled siRNAs to enhance therapeutic efficacy in drug-resistant ovarian cancer cells. J Am Chem Soc. 2014; 136(14):5181-4. PMC: 4210117. DOI: 10.1021/ja4098862. View