In Silico approach: Design an Optimized shRNA against RUNX1 Gene to Target HIV.

Rezvan Kakavand-Ghalehnoei, Elham Patrad, Mehrdad Ravanshad
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Abstract

Introduction: 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.

Methods: Several computational methods, including target alignment, similarity search, and secondary structure prediction, have been employed in the design of shRNA against RUNX1.

Results: Seven shRNA molecules with the highest efficiency were designed and validated using computational methods to silence the RUNX1 gene.

Conclusions: 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.

硅学方法:设计一种针对 RUNX1 基因的优化 shRNA 来靶向 HIV。
导言:人类免疫缺陷病毒(HIV)是一种具有单链 RNA 的逆转录病毒,会导致获得性免疫缺陷综合征(AIDS)这一具有挑战性的疾病。联合抗逆转录病毒疗法(cART)可以防止病情恶化,但无法长期根除艾滋病毒。治疗 HIV-1 感染者的重大障碍之一是在感染早期形成潜伏细胞库。利用 RNA 干扰(RNAi)抑制宿主或病毒基因表达的基因疗法被认为是很有前景的治疗方法。研究表明,T 细胞特异性转录因子 RUNX1 可能会对 HIV 复制和感染产生重大影响。根据干扰 RNA 技术在抑制基因表达方面作用的不断积累的证据,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 shRNAs,以靶向 HIV-1 的复制。 方法:在设计针对 RUNX1 的 shRNA 时采用了多种计算方法,包括目标配准、相似性搜索和二级结构预测。 结果利用计算方法设计并验证了七种效率最高的 shRNA 分子,可用于沉默 RUNX1 基因。 结论:在本研究中,我们设计了针对 RUNX1 的 shRNA,它可以靶向感染 HIV 的潜伏细胞。通过 shRNA 抑制 RUNX1 会重新激活潜伏细胞中的 HIV,从而增强免疫反应,准确识别病毒感染细胞。这一过程可有效减少感染艾滋病毒的细胞储库数量。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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