Recombinase RecHTLV Shows Promise in Targeting HTLV-1 Genome

Researchers from TU Dresden, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), and the company PROVIREX Genome Editing Therapies made initial progress in developing a potential therapeutic approach for the Human T-cell leukemia virus type 1 (HTLV-1) using gene-editing techniques.

The virus causes adult T-cell leukemia/lymphoma, HTVL-1-associated myelopathy, and other inflammatory diseases that can be fatal in up to 10% of carriers. Approximately 10 to 20 million people worldwide are infected with the HTLV-1 virus, with more than 90% of infections transmitted through sexual contact or breast milk. 

Currently, infected mothers are advised to stop or reduce breastfeeding, which increases the risk of other life-threatening diseases in poorer regions. The study published in Molecular Therapy shows that a designer recombinase, RecHTLV, can remove the virus from the DNA of infected cells in the laboratory.

Unlike the well-known CRISPR-Cas9 method, the gene scissors created in the lab are based on an enzyme called recombinase. RecHTLV was able to impede infection in cells where the virus had not yet fully integrated, and continuous improvements with designer recombinases have already been achieved concerning the HIV virus.

Further adaptation is required for RecHTLV to target HTLV-1, which also belongs to the retroviruses and behaves similarly to HIV. The researchers suggest that even if they only succeeded in lowering the viral load in patients, it would significantly reduce the risk of severe diseases for patients.

The enzyme RecHTLV can be produced under laboratory conditions and is introduced into infected cells using vectors. RecHTLV targets two specific identical DNA sequences of the virus found at the junction between the virus and human DNA and cuts at these sequences, thereby reversing the integration.

The study is a promising proof of concept, and the early successes have motivated researchers to continue working until they get HTLV-1 under control. As knowledge of a potential therapy could reduce the psychological stress of being infected, the researchers hope to further adapt RecHTLV for the HTLV-1 virus to achieve successful therapeutic outcomes.