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<p>Despite four decades of effort, neither a cure nor a preventive vaccine exists for HIV-1. HIV-1 vaccine development faces persistent barriers, including the rapid mutation rate of the virus, its genetic diversity, immune evasion strategies and the establishment of latent reservoirs. Although antiretroviral therapies effectively suppress replication, limitations such as lifelong adherence, drug resistance and inability to eliminate reservoirs underscore the need for novel vaccines. Critically, the foremost challenge in HIV-1 vaccines remains the induction of broadly neutralizing antibodies — a hurdle rooted in the virus’s structural complexity and host immune tolerance. mRNA technology offers rapid scalability, favourable safety profiles (avoiding viral vector-associated risks) and the capacity to elicit potent immune responses, possibly positioning mRNA-based medicine as a&#xa0;potential solution to the challenges posed by HIV-1. Additionally, mRNA enables swift iteration of immunogen designs, potentially accelerating broadly neutralizing antibody-focused strategies. Preclinical studies and early-phase clinical trials are actively exploring mRNA technology&#xa0;to overcome obstacles in HIV-1 immunization. In this Review, we explore mRNA technology, evaluate clinical trials of HIV-1 mRNA medicine and discuss persistent challenges in the development of mRNA-based interventions against HIV-1.</p>

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mRNA technology for the prevention and treatment of HIV-1 infection

  • 期刊论文

  • 发表日期：

    2026年1月9日

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  • Chuang Liu,
  • Alexey V. Yaremenko,
  • Xiaolong Li,
  • Xinru You,
  • Xiaoyu Zhu,
  • Nuo Liu,
  • Wei Chen,
  • Na Kong,
  • Tian Xie,
  • Gaurav D. Gaiha,
  • Robert Langer,
  • Wei Tao

摘要

Despite four decades of effort, neither a cure nor a preventive vaccine exists for HIV-1. HIV-1 vaccine development faces persistent barriers, including the rapid mutation rate of the virus, its genetic diversity, immune evasion strategies and the establishment of latent reservoirs. Although antiretroviral therapies effectively suppress replication, limitations such as lifelong adherence, drug resistance and inability to eliminate reservoirs underscore the need for novel vaccines. Critically, the foremost challenge in HIV-1 vaccines remains the induction of broadly neutralizing antibodies — a hurdle rooted in the virus’s structural complexity and host immune tolerance. mRNA technology offers rapid scalability, favourable safety profiles (avoiding viral vector-associated risks) and the capacity to elicit potent immune responses, possibly positioning mRNA-based medicine as a potential solution to the challenges posed by HIV-1. Additionally, mRNA enables swift iteration of immunogen designs, potentially accelerating broadly neutralizing antibody-focused strategies. Preclinical studies and early-phase clinical trials are actively exploring mRNA technology to overcome obstacles in HIV-1 immunization. In this Review, we explore mRNA technology, evaluate clinical trials of HIV-1 mRNA medicine and discuss persistent challenges in the development of mRNA-based interventions against HIV-1.