CRISPR 编辑的干细胞移植用于体内 HIV 相关基因修饰：系统评价。

CRISPR-Edited Stem Cell Transplantation for HIV-Related Gene Modification In Vivo: A Systematic Review.

机构信息

Department of Biotechnology, College of Health Science, Asia University, Taichung, 41354, Taiwan.

Graduate Institute of Biomedical Sciences, China Medical University, Taichung, 40402, Taiwan.

出版信息

Stem Cell Rev Rep. 2022 Jun;18(5):1743-1755. doi: 10.1007/s12015-022-10345-9. Epub 2022 Feb 15.

DOI:10.1007/s12015-022-10345-9

PMID:35169967

Abstract

BACKGROUND

CRISPR is a novel genomic editing technology which can be useful for the treatment of immune diseases such as HIV. However, the application of CRISPR in stem cells for HIV-related research was not effective, and most of the research was done in vivo. This systematic review is to identify a new research idea about increase CRISPR-editing efficiencies in stem cell transplantation for HIV treatment, as well as its future perspective.

METHOD

Four databases were searched for articles published during 1952 to 2020. PRISMA method was used to select appropriate research papers. CAMARADES was used to identify the paper quality. The outcome was engraftment efficiency, gene disruption percentage, differentiation ability, HIV-resistant efficiency.

RESULT

Screening method showed 196 papers mentioned the topic. However, only 5 studies were reliable with the research objective. We found that (1) Two research ideas which was double gene knockout and knockout-knockin method to provide HIV-resistant cells, engraftment support and avoid cardiac disease as an HIV disease side effect. (2) Ribonucleoprotein (RNP) delivery was the best way to deliver the CRISPR/Cas9 and Adeno-Associated Virus (AAV) would be effective for knockin purpose. (3) CRISPR/SaCas9 could replace CRISPR/Cas9 role in editing HIV-related gene.

CONCLUSION

Potential genes to increase HIV resistance and stem cell engraftment should be explored more in the future. Double knockout and knock-in procedures should be applied to set up a better engraftment for improving HIV treatment or resistance of patients. CRISPR/SaCas9 and RNP delivery should be explored more in the future.

SYSTEMATIC REVIEW REGISTRATION

PROSPERO CRD42020203312.

摘要

背景

CRISPR 是一种新型基因组编辑技术，可用于治疗 HIV 等免疫性疾病。然而，CRISPR 在干细胞中的应用在 HIV 相关研究中效果不佳，且大多数研究都是在体内进行的。本系统评价旨在确定一种新的研究思路，即提高 HIV 治疗中干细胞移植的 CRISPR 编辑效率及其未来展望。

方法

检索了 1952 年至 2020 年期间发表的文章，共 4 个数据库。采用 PRISMA 方法选择合适的研究论文。CAMARADES 用于识别论文质量。结果是嵌合效率、基因敲除率、分化能力、HIV 抗性效率。

结果

筛选方法显示有 196 篇文章提到了这个话题。然而，只有 5 项研究与研究目标相符。我们发现：（1）两种研究思路，即双基因敲除和敲入敲除方法，为提供 HIV 抗性细胞、移植支持并避免作为 HIV 疾病副作用的心脏病提供了可能；（2）核糖核蛋白（RNP）递送是递送 CRISPR/Cas9 的最佳方法，腺相关病毒（AAV）将有效用于敲入目的；（3）CRISPR/SaCas9 可以替代 CRISPR/Cas9 在编辑 HIV 相关基因中的作用。