Abstract

Introduction

: Antiretroviral therapy (ART) has transformed prognoses for HIV-1-infected individuals but requires lifelong adherence to prevent viral resurgence. Targeted elimination or permanent deactivation of the latently infected reservoir harboring integrated proviral DNA, which drives viral rebound, is a major focus of HIV-1 research.

Areas covered

This review covers the current approaches to developing curative strategies for HIV-1 that target the latent reservoir. Discussed herein are shock and kill, broadly neutralizing antibodies (bNAbs), block and lock, Chimeric antigen receptor (CAR) T cells, immune checkpoint modulation, clustered regularly interspaced short palindromic repeats (CRISPR) / CRISPR-associated protein 9 (Cas9) coreceptor ablation, and CRISPR/Cas9 proviral excision. Emphasis in this review is placed on CRISPR/Cas9 proviral excision/inactivation. Recent advances and future directions towards discovery and translation of HIV-1 therapeutics are discussed.

Expert opinion

CRISPR/Cas9 proviral targeting fills a niche amongst HIV-1 cure strategies by directly targeting the integrated provirus without the necessity of an innate or adaptive immune response. Each strategy discussed in this review has shown promising results with the potential to yield curative or adjuvant therapies. CRISPR/Cas9 is singular among these in that it addresses the root of the problem, integrated proviral DNA, with the capacity to permanently remove or deactivate the source of HIV-1 recrudescence.

中文翻译：

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HIV-1治愈策略：为什么选择CRISPR？

摘要

介绍

：抗逆转录病毒疗法（ART）改变了HIV-1感染者的预后，但需要终身坚持以防止病毒复发。HIV-1研究的主要重点是靶向清除或永久灭活带有整合前病毒DNA的潜伏感染病毒库，该病毒可驱动病毒反弹。

覆盖区域

这篇综述涵盖了针对潜伏水库的HIV-1治疗策略的当前开发方法。本文讨论的是休克和杀伤，广泛中和抗体（bNAb），阻断和锁定，嵌合抗原受体（CAR）T细胞，免疫检查点调节，成簇规则间隔的短回文重复序列（CRISPR）/ CRISPR相关蛋白9（Cas9）核心受体消融和CRISPR / Cas9前病毒切除。本文的重点是CRISPR / Cas9前病毒切除/灭活。讨论了发现和翻译HIV-1治疗剂的最新进展和未来方向。

专家意见

CRISPR / Cas9前病毒靶向通过直接靶向整合的前病毒而无需先天或适应性免疫反应，从而填补了HIV-1治愈策略中的一个空白。本综述中讨论的每种策略均显示出令人鼓舞的结果，并可能产生治愈性或辅助性疗法。CRISPR / Cas9在其中很独特，因为它解决了问题的根源，即整合的前病毒DNA，具有永久去除或灭活HIV-1复发源的能力。