Document Type
STEM
Date
2024
Submission Date
January 2024
Abstract
Human Immunodeficiency Virus (HIV) is a retrovirus that infects CD4+ T cell lymphocytes in humans, leading to the development of Acquired Immunodeficiency Syndrome (AIDS) if left untreated. While current treatment methods, including antiretroviral combination treatments, effectively limit HIV replication, HIV can evade these treatments due to its high mutation rate. Long-term antiretroviral treatment can also be toxic to patients, meaning patients would benefit from a new mechanism of HIV treatment. RNA interference (RNAi) is an antiviral pathway found in mammals, plants, and insects that involves a small-interfering RNA that is incorporated into a protein complex called the RNA-induced Silencing Complex (RISC). This complex binds to and cleaves viral mRNAs, reducing viral gene expression. RNAi is a promising method of treating HIV/AIDS, since it has been found to adapt to and target highly-conserved sequences in Hepatitis C Virus, A549 lung cancer, and SARS-CoV-2 in mammalian cells. Patisiran is an FDA-approved RNAi treatment for use in humans, making an HIV RNAi treatment plausible. However, an RNAi treatment for HIV has not yet been designed or developed. This paper aims to propose a comprehensive potential RNAi treatment for HIV. RNAi may effectively inhibit HIV replication by containing two siRNAs with the sequences 5’-UUAAUACUGACGCUCUCGC-3’ and 5’-UGUAUUGAUAGAUAACUAU-3’ that target the highly-conserved p17 and Reverse Transcriptase genes, respectively, delivered within a solid lipid nanoparticle composed of equimolar amounts of DOTAP and DODMA cationic lipids and containing LFA-1 antibody on the surface for receptor-mediated endocytosis, and cotransported with Rev and GagPol HIV proteins to limit the anti-RNAi function of HIV’s RRE and TAR.
Rights
© The Author(s)
Is Part Of
Auctus
DOI
https://doi.org/10.25886/jmzp-h010