Summary
A bioRxiv preprint reports that CRISPR-Cas13X.1 targeting the HIV-1 TAR RNA element reduced viral gene expression and reactivation in laboratory models. The findings include experiments in HIV-infected primary immune cells, but are preclinical.
A bioRxiv preprint reports that researchers used CRISPR-Cas13X.1 to target an HIV-1 RNA element, reducing viral gene expression and reactivation in laboratory models. The work focuses on the transactivation response (TAR) element, which is required for Tat-dependent HIV transcription. Experiments also found reduced viral load in HIV-1-infected primary peripheral blood mononuclear cells (PBMCs), a type of immune cell.
The findings are preclinical: the reported evidence comes from infection and latency models, including experiments in infected cells, rather than clinical testing in people.
Why target HIV-1 TAR?
HIV can persist in a latent state in cells, with viral activity suppressed, and later resume gene expression. This persistence is a major obstacle to a cure. When HIV-1 is transcribed, TAR is an RNA element in the virus’s 5′ untranslated region (5′UTR). The researchers focused on TAR because it participates in the interaction with Tat, a viral protein needed for efficient Tat-dependent transcription.
Cas13 systems use a CRISPR RNA, or crRNA, to direct the Cas13 protein to a matching RNA sequence. In this study, the researchers developed a hypercompact Cas13X.1 system and validated a single-vector setup. They screened crRNAs aimed at different elements in the HIV-1 5′UTR. Among those tested, crRNA-TAR-2 most strongly inhibited Tat-dependent reporter activity. Mechanistic analyses indicated that targeting TAR disrupted the Tat–TAR interaction.
Results across infection and latency models
In HIV-1 infection models, TAR targeting reduced levels of the viral Gag precursor protein p55 and capsid protein p24. The researchers also reported lower levels of gag and tat transcripts, alongside activation of the PKR-eIF2α antiviral pathway.
The team found that TAR targeting suppressed viral gene expression and reactivation in multiple HIV latency models. In experiments with HIV-1-infected primary PBMCs, it also reduced viral load. The preprint abstract does not provide numerical effect sizes or detailed descriptions of the individual models, so the reported outcomes cannot be compared quantitatively from that summary.
The results identify HIV-1 TAR RNA as a target for Cas13X.1-mediated antiviral activity and support further study of RNA-targeting CRISPR systems. They do not establish a treatment for people: the reported work is experimental research in infection and latency models. The preprint was posted on bioRxiv on October 15, 2026.