Gene editing toward the use of autologous therapies in recessive dystrophic epidermolysis bullosa

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• 作者：Christopher Perdoni^a ; ^b ; Mark J. Osborn^a ; ^b ; Jakub Tolar^a ; ^b ; ^{morga336@umn.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：AAV ; adeno-associated virus ; AF ; anchoring fibril ; BMZ ; basement membrane zone ; C7 ; type VII collagen protein ; CRISPR ; clustered regularly interspaced short palindromic repeats ; DEJ ; dermal-epidermal junction ; gRNA ; guide RNA ; HCT ; hematopoietic cell transplantation ; iPSC ; induced pluripotent stem cell ; LV ; lentiviral ; MSC ; mesenchymal stem cell ; PAM ; protospacer adjacent motif ; PTCs ; premature termination codons ; RDEB ; recessive dystrophic epidermolysis bullosa ; RV ; retroviral ; RVDs ; repeat var
• 刊名：Translational Research
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：168
• 期：Complete
• 页码：50-58
• 全文大小：279 K

文摘

Recessive dystrophic epidermolysis bullosa (RDEB) is a disease caused by mutations in the COL7A1 gene that result in absent or dysfunctional type VII collagen protein production. Clinically, RDEB manifests as early and severe chronic cutaneous blistering, damage to internal epithelium, an increased risk for squamous cell carcinoma, and an overall reduced life expectancy. Recent localized and systemic treatments have shown promise for lessening the disease severity in RDEB, but the concept of ex vivo therapy would allow a patient's own cells to be engineered to express functional type VII collagen. Here, we review gene delivery and editing platforms and their application toward the development of next-generation treatments designed to correct the causative genetic defects of RDEB.