Kakavand-Ghalehnoei Rezvan, Patrad Elham, Ravanshad Mehrdad
Department of Virology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Cancer Research Center, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran.
Curr Drug Discov Technol. 2025;22(3):e250424229316. doi: 10.2174/0115701638291312240415151051.
Human Immunodeficiency Virus (HIV) is a retrovirus with single-stranded RNA that leads to the challenging disease of acquired immunodeficiency syndrome (AIDS). Combination antiretroviral therapy (cART) can prevent the progression of the disease, but it is not capable of long-term HIV elimination. One of the significant obstacles to treating HIV-1-infected individuals is the creation of latent cell reservoirs early in the infection. Gene-based therapies that utilize RNA interference (RNAi) to silence host or viral gene expression are considered promising therapeutic approaches. It has been demonstrated that RUNX1, a T-cell-specific transcription factor, may significantly affect HIV replication and infection. According to accumulating evidence on the role of interfering RNA techniques in inhibiting gene expression and considering the role of RUNX1 in the replication of HIV-1. In this study, we aim to design shRNAs against RUNX1 that can target the replication of HIV-1.
Several computational methods, including target alignment, similarity search, and secondary structure prediction, have been employed in the design of shRNA against RUNX1.
Seven shRNA molecules with the highest efficiency were designed and validated using computational methods to silence the RUNX1 gene.
In the present study, we designed shRNA against RUNX1, which can target latent cells infected with HIV. Suppression of RUNX1 by shRNA reactivates HIV in the latent cells and subsequently potentiates the immune response toward identifying accurate virus-infected cells. This process may lead to an effective and efficient reduction of the volume of cell reservoirs infected with HIV.
人类免疫缺陷病毒（HIV）是一种单链RNA逆转录病毒，可导致具有挑战性的获得性免疫缺陷综合征（AIDS）。联合抗逆转录病毒疗法（cART）可以预防疾病进展，但无法长期消除HIV。治疗HIV-1感染个体的一个重大障碍是在感染早期形成潜伏细胞库。利用RNA干扰（RNAi）沉默宿主或病毒基因表达的基因疗法被认为是有前景的治疗方法。已经证明，RUNX1，一种T细胞特异性转录因子，可能会显著影响HIV复制和感染。根据关于干扰RNA技术在抑制基因表达中的作用的越来越多的证据，并考虑到RUNX1在HIV-1复制中的作用。在本研究中，我们旨在设计针对RUNX1的短发夹RNA（shRNA），其可以靶向HIV-1的复制。
在设计针对RUNX1的shRNA时采用了几种计算方法，包括靶点比对、相似性搜索和二级结构预测。
设计了七个效率最高的shRNA分子，并使用计算方法进行验证以沉默RUNX1基因。
在本研究中，我们设计了针对RUNX1的shRNA，其可以靶向感染HIV的潜伏细胞。shRNA对RUNX1的抑制会重新激活潜伏细胞中的HIV，并随后增强针对识别准确病毒感染细胞的免疫反应。这一过程可能导致有效且高效地减少感染HIV的细胞库的体积。
