Universidade de São Paulo, Faculdade de Medicina, Divisão de Dermatologia, Laboratório de Investigação Médica LIM-56, São Paulo, São Paulo, Brazil.
Rev Inst Med Trop Sao Paulo. 2024 Aug 26;66:e48. doi: 10.1590/S1678-9946202466048. eCollection 2024.
The human T-cell lymphotropic virus type 1 (HTLV-1) is a single-stranded positive-sense RNA virus that belongs to the Retroviridae family, genus Deltaretro, and infects approximately five to 10 million people worldwide. Although a significant number of individuals living with HTLV-1 remain asymptomatic throughout their lives, some develop one or more severe clinical conditions, such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a progressive and debilitating disease, and/or a subtype of non-Hodgkin's lymphoma with a more threatening course known as adult T-cell leukemia/lymphoma (ATLL). Moreover, current therapeutic options are limited and focus primarily on treating symptoms and controlling viral latency. CRISPR-Cas9 gene editing is proposed as a promising tool to address the intricate links associated with HTLV-1. By targeting or silencing key genes during initial infection and dysregulating immune signaling pathways, CRISPR-Cas9 offers potential intervention opportunities. In this review, we address the therapeutic potential of CRISPR-Cas9 gene editing, as well as examine the primary mechanisms involved in editing potential target genes and discuss the existing evidence in the current scientific literature.
人类 T 细胞嗜淋巴细胞病毒 1 型（HTLV-1）是一种单链正链 RNA 病毒，属于逆转录病毒科、δ逆转录病毒属，感染全球约 500 万至 1000 万人。尽管大量携带 HTLV-1 的个体终生无症状，但仍有部分人会发展出一种或多种严重的临床病症，如 HTLV-1 相关性脊髓病/热带痉挛性截瘫（HAM/TSP），这是一种进行性和使人虚弱的疾病，以及/或一种更具威胁性的非霍奇金淋巴瘤亚型，称为成人 T 细胞白血病/淋巴瘤（ATLL）。此外，目前的治疗选择有限，主要集中在治疗症状和控制病毒潜伏期。CRISPR-Cas9 基因编辑被提议作为解决与 HTLV-1 相关的复杂联系的有前途的工具。通过在初始感染时靶向或沉默关键基因并调节免疫信号通路，CRISPR-Cas9 提供了潜在的干预机会。在这篇综述中，我们探讨了 CRISPR-Cas9 基因编辑的治疗潜力，以及检查编辑潜在靶基因所涉及的主要机制，并讨论当前科学文献中的现有证据。
