Lymphoid and CXCR4 Cell Targeted Lipid Nanoparticles Facilitate HIV-1 Proviral DNA Excision.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 40653915.
- Also identified by DOI 10.1002/adhm.202501190 and PMC identifier 12477575.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Advancements in antiretroviral therapy (ART) enable those living with the human immunodeficiency virus type one (HIV-1) to lead longer, healthier lives free from disease comorbidities. However, lifelong ART poses challenges. These include social stigma, medication costs, drug accessibility, mental health, and drug-related toxicities. Moreover, ART does not eliminate latent HIV-1 DNA. Viral persistence in tissue and cell reservoirs results in viral rebound after ART interruption. New strategies are required to achieve a functional HIV-1 cure. To excise latent HIV-1, C-X-C motif chemokine receptor 4 (CXCR4) ligand-decorated lymphoid tissue-targeting lipid nanoparticles (LNPs) for CRISPR-Cas9/gRNA delivery are developed. These LNPs enhance mRNA translation and demonstrate CXCR4-mediated improved uptake to eliminate HIV-1 DNA in infected CD4+ T cells. LNPs also facilitate targeted drug delivery, achieving HIV-1 DNA excision in ART-treated, infected humanized mice. This study emphasizes the potential of tissue and cell-targeted LNPs for effective HIV-1 DNA excision.
Medical subject headings
- Receptors, CXCR4
- HIV-1
- Nanoparticles
- DNA, Viral
- Lipids
- Proviruses