期刊
BIOMATERIALS
卷 258, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2020.120282
关键词
Genome editing; TALENs; CRISPR-Cas9; Gene knockout; Knock-in; Non-viral physical and chemical methods; Organic and inorganic delivery systems; Non-clinical studies; Clinical trials
资金
- Russian Foundation for Basic Research [19-29-04025]
- Russian Science Foundation [20-45-01012]
- DZIF/TTU HIV
- Tomsk Polytechnic University Competitiveness Enhancement Program
- [DFG/SFB841/SP2]
- Russian Science Foundation [20-45-01012] Funding Source: Russian Science Foundation
Besides its broad application in research and biotechnology, genome editing (GE) has great potential for clinical gene therapy, but delivery of GE tools remains a bottleneck. Whereas significant progress has been made in ex vivo GE delivery (e.g., by electroporation), establishment of efficient and safe in vivo delivery systems is still a challenge. Above and beyond standard vector requirements (safety, minimal/absent toxicity and immunogenicity, sufficient packaging capacity, targeting, straight and low-cost large-scale good manufacturing practice (GMP) production), GE delivery systems ideally use a hit-and-run principle to minimize off-targets as well as display of immunogenic peptides. Since currently used viral vectors do not fulfil all of these requirements, the broad variety of non-viral delivery platforms represents a promising alternative. This review provides a comprehensive analysis of the most relevant aspects of non-viral physical and chemical delivery methods in non-clinical studies and clinical trials, ranging from classic electroporation to advanced drug carriers that can transport GE tools in form of plasmid DNAs (pDNAs), mRNAs, and ribonucleoproteins (RNPs). For comparison, advantages and shortcomings of viral delivery systems are shortly discussed. In summary, we review various delivery approaches and discuss the future perspectives to use drug carriers for in vivo GE in clinical trials.
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