Novel Genome-Editing Tools to Model and Correct Primary Immunodeficiencies.
Novel Genome-Editing Tools to Model and Correct Primary Immunodeficiencies.
复制标题
DOI：
10.3389/fimmu.2015.00250
复制
发表时间：
2015
影响因子：
7.3
通讯作者：
Musunuru K
中科院分区：
文献类型：
--
作者：
Ott de Bruin LM;Volpi S;Musunuru K
严重联合免疫缺陷（SCID）和其他严重非 SCID 原发性免疫缺陷（非 SCID PID）可以通过同种异体造血干细胞（HSC）移植来治疗，但当缺乏组织相容性白细胞抗原匹配供体时，这可能是一个高风险的手术。通过基因疗法纠正患者自身的造血干细胞提供了一种有吸引力的替代方案。目前临床使用的基因疗法通过病毒载体插入整个基因的功能副本。通过这种治疗，由于癌基因内的整合可能会导致严重的并发症。一种有前景的替代方案是使用 ZFN、TALEN 和 CRISPR/Cas9 等核酸内切酶在 DNA 中引入双链断裂，从而诱导同源定向修复。借助这些基因组编辑工具，可以将正确的副本插入精确定位的“安全港”。它们还可用于纠正原位致病突变，并开发研究免疫缺陷患者中发现的特定遗传缺陷的致病影响所需的细胞或动物模型。这篇综述讨论了这些核酸内切酶在基因校正和建模中的优点和缺点，重点是 CRISPR/Cas9，它因其功效和多功能性而最具前景。
Severe combined immunodeficiency (SCID) and other severe non-SCID primary immunodeficiencies (non-SCID PID) can be treated by allogeneic hematopoietic stem cell (HSC) transplantation, but when histocompatibility leukocyte antigen-matched donors are lacking, this can be a high-risk procedure. Correcting the patient’s own HSCs with gene therapy offers an attractive alternative. Gene therapies currently being used in clinical settings insert a functional copy of the entire gene by means of a viral vector. With this treatment, severe complications may result due to integration within oncogenes. A promising alternative is the use of endonucleases such as ZFNs, TALENs, and CRISPR/Cas9 to introduce a double-stranded break in the DNA and thus induce homology-directed repair. With these genome-editing tools a correct copy can be inserted in a precisely targeted “safe harbor.” They can also be used to correct pathogenic mutations in situ and to develop cellular or animal models needed to study the pathogenic effects of specific genetic defects found in immunodeficient patients. This review discusses the advantages and disadvantages of these endonucleases in gene correction and modeling with an emphasis on CRISPR/Cas9, which offers the most promise due to its efficacy and versatility.
登录
查看更多内容
影响因子：
7.3
作者：
Al-Herz W;Bousfiha A;Casanova JL;Chatila T;Conley ME;Cunningham-Rundles C;Etzioni A;Franco JL;Gaspar HB;Holland SM;Klein C;Nonoyama S;Ochs HD;Oksenhendler E;Picard C;Puck JM;Sullivan K;Tang ML
通讯作者：
Tang ML
影响因子：
7
作者：
Cho SW;Kim S;Kim Y;Kweon J;Kim HS;Bae S;Kim JS
通讯作者：
Kim JS
影响因子：
20.3
作者：
Biffi, Alessandra;Bartholomae, Cynthia C.;Montini, Eugenio
通讯作者：
Montini, Eugenio
影响因子：
46.9
作者：
Cho, Seung Woo;Kim, Sojung;Kim, Jin-Soo
通讯作者：
Kim, Jin-Soo
影响因子：
4.4
作者：
Buckley, Rebecca H.
通讯作者：
Buckley, Rebecca H.