METHODS AND COMPOSITIONS FOR RNA-GUIDED TREATMENT OF HIV INFECTION

Smart overview of the Invention

The patent application describes a method for preventing the transmission of HIV from a mother to her offspring using a CRISPR-Cas9 based approach. This method involves administering a composition that includes a CRISPR-associated endonuclease and multiple guide RNAs (gRNAs) targeting distinct sequences in the HIV proviral DNA. The goal is to excise the entire HIV-1 proviral genome, thereby eradicating the virus from the host cell and preventing its transmission to offspring.

Technical Background

HIV/AIDS remains a significant global health issue due to the virus's ability to integrate into the host genome, making it difficult to cure. Current therapies like HAART reduce viral replication but do not eliminate latent viral reservoirs or fully suppress viral genome expression. These persistent infections contribute to various co-morbidities and highlight the need for new therapeutic strategies targeting latent viral reservoirs.

Invention Details

The invention leverages CRISPR-Cas9 technology to specifically target and excise integrated HIV-1 proviral DNA from infected cells. The method employs gRNAs complementary to sequences in the long terminal repeats (LTRs) of HIV-1, allowing for precise editing without harming host cells. This approach not only inactivates viral gene expression but also prevents new infections by eliminating the virus's genetic material.

Clinical Implications

This CRISPR-based treatment could be administered at any stage of HIV infection or as a preventive measure in at-risk individuals. It offers a potential means of excising integrated HIV proviral DNA, thereby reducing or eliminating viral replication and preventing transmission, even when combined with existing antiretroviral therapies.

Compositional Features

The compositions include nucleic acids encoding CRISPR-associated endonucleases like Cas9 and guide RNAs targeting specific sequences in HIV. Cas9, part of the type II CRISPR system, uses guide RNA to locate and cut target DNA sequences. This system can be engineered using synthetic small guide RNAs (sgRNAs) to mimic natural RNA structures, providing a versatile tool for precise genetic editing.