Bhat Prashant, Garibyan Lilit
David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, USA.
JID Innov. 2022 Jan 25;2(2):100103. doi: 10.1016/j.xjidi.2022.100103. eCollection 2022 Mar.
Over the past decade, CRISPR has rapidly made its way from the bench to the bedside, providing a newfound therapeutic avenue to not only treat genetic diseases but also permanently cure them. Although there are several clinical trials in early stages, there are so far no CRISPR-based clinical trials for cutaneous disease. In this review, we describe multiple cutaneous diseases that represent ideal targets for CRISPR-based therapeutics owing to known single gene‒causing mutations. We also explore the potential of CRISPR nucleases to treat inflammatory disorders such as eczema and psoriasis, which are not classically categorized as genodermatoses. We describe the therapeutic solutions for these diseases that are guided by various CRISPR-associated (Cas) effector proteins, for example, using Cas9 to permanently edit the DNA of somatic cells, Cas3 to target foreign DNA to combat viral/bacterial skin infections, and Cas13 to edit mutated RNA transcripts in diseases where permanent DNA editing is untenable. Furthermore, we discuss various drug delivery modalities for CRISPR therapeutics, including transdermal patches and microneedles, which are uniquely suited for dermatological diseases. In summary, we highlight the potential of CRISPR-based therapeutics to revolutionize the treatment of cutaneous disease with a goal of being accessible to the practicing dermatologist.
在过去十年中，CRISPR技术迅速从实验室走向临床，为治疗遗传性疾病乃至实现永久性治愈开辟了一条全新的治疗途径。尽管目前有多项临床试验尚处于早期阶段，但迄今为止，尚无基于CRISPR技术针对皮肤疾病的临床试验。在本综述中，我们描述了多种由于已知单基因突变导致的皮肤疾病，这些疾病是基于CRISPR技术治疗的理想靶点。我们还探讨了CRISPR核酸酶治疗炎症性疾病（如湿疹和银屑病）的潜力，这些疾病传统上并不归类为遗传性皮肤病。我们描述了由各种CRISPR相关（Cas）效应蛋白指导的针对这些疾病的治疗方案，例如，使用Cas9永久编辑体细胞的DNA，使用Cas3靶向外来DNA以对抗病毒/细菌性皮肤感染，以及在无法进行永久性DNA编辑的疾病中使用Cas13编辑突变的RNA转录本。此外，我们讨论了CRISPR治疗的各种药物递送方式，包括透皮贴剂和微针，它们特别适用于皮肤病。总之，我们强调了基于CRISPR技术的治疗方法在彻底改变皮肤疾病治疗方面的潜力，目标是让皮肤科执业医生能够应用。
