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Collaborative project to develop novel therapeutic strategies against the human immunodeficiency virus (HIV)
Hamburg. A research team led by Dr. Dr. Ulrike Lange, head of the LIV-BMBF junior research group Genomics of Retroviral Infections, Prof. Priti Kumar from Yale University and Prof. Melanie Ott from the Gladstone Institutes has been awarded a five-year NIH (National Institutes of Health) grant worth 2.79 million US dollars for the development of an innovative gene therapy that can inactivate the HIV provirus in infected immune cells. Of this, 1.03 million US dollars will go to the laboratory of Dr. Dr. Ulrike Lange at the Leibniz Institute of Virology (LIV).
Despite the effectiveness of antiretroviral therapy (ART), people living with HIV retain a reservoir of infected cells with inactive virus. Interrupting therapy can quickly lead to a resurgence of the infection throughout the body. HIV research is therefore focusing on possible strategies to inactivate or eliminate the viral reservoir.
The collaborative research team is pursuing this goal by developing a novel in vivo gene therapy based on two innovative approaches:
Firstly, the HIV-specific designer DNA recombinase Brec1 is used. This technology, developed at the LIV and TU Dresden and marketed by PROVIREX, enables the targeted removal of HIV-1 viruses from the genome of infected reservoir cells. The research team is now working on a further development of Brec1 in the form of a super-repressor, which does not remove the HIV-1 provirus, but inactivates it specifically through epigenetic changes and thereby silences it.
Secondly, a central point is the use of novel capsid-optimized AAV vectors, which are used in in vivo gene therapy for delivery to target cells. AAV vectors are known for their safety in clinical gene therapy, but their targeted delivery still needs to be optimized. The research team will develop AVV vectors that can reach human T and myeloid as HIV reservoir cells in peripheral tissues as well as in the central nervous system.
"The results of this collaborative research project could lay the foundation for clinical trials and present an important step towards an ART-free, cure-like therapy for people with HIV," explains Dr. Dr. Ulrike Lange.
The funding period for the project entitled "Capsid-engineered AAV vectors with Brec1-based gene therapeutics for inactivating the HIV reservoir" (award number: R01AI181053) runs from July 2024 to June 2029.
Dr. Dr. Ulrike Lange ulrike.lange@leibniz-liv.de
https://www.leibniz-liv.de/en/ LIV website
Dr. Dr. Ulrike Lange
Gisela Köhler
LIV, Gisela Köhler
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