Agbosu Esinam E, Ledger Scott, Kelleher Anthony D, Wen Jing, Ahlenstiel Chantelle L
Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia.
RNA Institute, University of New South Wales, Sydney, NSW 2052, Australia.
Pharmaceutics. 2022 Jun 26;14(7):1352. doi: 10.3390/pharmaceutics14071352.
Our understanding of HIV infection has greatly advanced since the discovery of the virus in 1983. Treatment options have improved the quality of life of people living with HIV/AIDS, turning it from a fatal disease into a chronic, manageable infection. Despite all this progress, a cure remains elusive. A major barrier to attaining an HIV cure is the presence of the latent viral reservoir, which is established early in infection and persists for the lifetime of the host, even during prolonged anti-viral therapy. Different cure strategies are currently being explored to eliminate or suppress this reservoir. Several studies have shown that a functional cure may be achieved by preventing infection and also inhibiting reactivation of the virus from the latent reservoir. Here, we briefly describe the main HIV cure strategies, focussing on the use of RNA therapeutics, including small interfering RNA (siRNA) to maintain HIV permanently in a state of super latency, and CRISPR gRNA to excise the latent reservoir. A challenge with progressing RNA therapeutics to the clinic is achieving effective delivery into the host cell. This review covers recent nanotechnological strategies for siRNA delivery using liposomes, N-acetylgalactosamine conjugation, inorganic nanoparticles and polymer-based nanocapsules. We further discuss the opportunities and challenges of those strategies for HIV treatment.
自1983年发现艾滋病毒以来，我们对艾滋病毒感染的认识有了很大进展。治疗方案改善了艾滋病毒/艾滋病感染者的生活质量，将这种致命疾病转变为一种慢性的、可控制的感染。尽管取得了所有这些进展，但治愈方法仍然难以捉摸。实现艾滋病毒治愈的一个主要障碍是潜伏病毒库的存在，它在感染早期就已形成，并在宿主的一生中持续存在，即使在长期抗病毒治疗期间也是如此。目前正在探索不同的治愈策略来消除或抑制这个病毒库。多项研究表明，通过预防感染以及抑制病毒从潜伏病毒库中重新激活，有可能实现功能性治愈。在此，我们简要描述主要的艾滋病毒治愈策略，重点关注RNA疗法的应用，包括使用小干扰RNA（siRNA）使艾滋病毒永久处于超级潜伏状态，以及使用CRISPR gRNA切除潜伏病毒库。将RNA疗法推进到临床面临的一个挑战是如何有效地递送至宿主细胞。本综述涵盖了近期使用脂质体、N-乙酰半乳糖胺缀合、无机纳米颗粒和基于聚合物的纳米胶囊进行siRNA递送的纳米技术策略。我们还进一步讨论了这些策略在艾滋病毒治疗方面的机遇和挑战。
