HIV gene-editing therapy heads to the clinic

HIV gene-editing therapy heads to the clinic

Provirex’ innovative genome editing therapy enables the elimination of persistent viral genomes from infected cells. Preparing for a clinical study, the start-up is building a therapy hub in the future Science City Hamburg Bahrenfeld.

Eliminate viral DNA with gene scissors

Even though enormous advances have been made in HIV treatment, the disease is still not fully curable. Nowadays, the propagation of the virus in the body can be held in check through medication, but the viral DNA (the provirus) remains present in body cells where it integrates in the genome.

By translating a powerful genome editing approach into clinical application, Hamburg-based start-up Provirex Genome Editing Therapies aims at revolutionizing the way HIV is treated – and even cured. The spin-off of the Leibniz Institute of Virology (LIV) is now preparing at Start-up Labs Bahrenfeld at DESY for a publicly funded clinical trial at the University Medical Center Hamburg-Eppendorf (UKE). Thanks to the support of two investors in 2022, they are now building up a large space at the emerging Science City Hamburg Bahrenfeld to establish a therapy hub.

A designer enzyme as precision medicine tool

The star of Provirex’ genome editing approach is a designer recombinase called Brec1. This enzyme is a programmable biomolecular scalpel that finds its target site in the genome and cuts out pieces of DNA with unparalleled precision. “Our recombinase works completely different than nucleases like CRISPR-Cas9, as it performs the complete genome surgical process without any errors or unwanted mutations left behind,” says Jan Chemnitz, one of the founders and CEO of Provirex. He was part of the research team developing the technology which is based on a long-term collaboration between now retired Professor Joachim Hauber and his team at LIV and Professor Frank Buchholz at the Technical University of Dresden.

The company’s broad technology and patent portfolio was built up over a period of more than 15 years in the participating research institutes and exclusively licensed to the company with the support of Ascenion as a technology transfer partner. Having the recombinase technology ready for clinical application is perfectly aligned with a biopharma sector that enjoys a booming field of gene and cell therapies. But getting to this point proved to be challenging for the innovators in Hamburg. Initially, some of the scientific community was skeptical about the feasibility of the approach, and investors’ interest in the clinical translation of the Brec1 technology was low. “We were ten years ahead of our time,” says Oliver Ahnfeld, co-founder and CEO of Provirex.

Public funding and relentless institutional support from LIV have enabled the researchers to go on and show that the technology is safe and efficient in animals, and to prepare the groundwork for clinical trials in humans. One major milestone was a publication in the acclaimed journal “Nature Biotechnology” in 2016. In this paper, the team demonstrated that Brec1 was capable of specifically removing the provirus from the infected cells of most primary HIV-1 isolates. “It means that 94% of HIV patients can be treated with our approach,” says Chemnitz.

The illustration shows how the recombinase Brec1 cuts the HIV provirus from the genome of a T cell. © Illustration SCIsytel for LIV
The illustration shows how the recombinase Brec1 cuts the HIV provirus from the genome of a T cell. © Illustration SCIsytel for LIV

Clinical study with engineered blood stem cells

With these promising results in hand, the LIV team started fundraising and successfully applied, with the UKE, to the Federal Ministry of Education and Research (BMBF) for multi-million euros’ worth of funding. The financial support would be used for a clinical trial named HIVCure. The Hamburg Senate invested another million euros for developing tools needed for the study. HIVCure, a first-in-human phase Ib/IIa clinical trial, is supposed to start at the UKE at the end of 2024. It aims to remove HIV-1 from infected subjects using gene editing of the patient’s peripheral blood stem cells. “The retransplanted engineered blood stem cells build up an immune system that is now resistant to HIV,” describes Chemnitz. He says Provirex also conducts research on the direct delivery of Brec1 by molecular ferries.

New investors giving a boost for a therapy hub

The start-up was founded in 2019 thanks to seed funding from the City of Hamburg. It received another major boost last year when

  • venture capitalist Bioventure Management
  • and IFB Innovationsstarter

invested in the enterprise. “This investment will provide financial security for the company over the next four years and help to build a therapy hub in the future Science City Hamburg Bahrenfeld,” says Ahnfeld. In 2024 the new lab, occupying an area of about 500 sqm, is due to be finished. In specially designed cleanrooms, advanced therapy medicinal products (ATMP) will be produced, while meeting the safety standards for working with human viruses. “In the long term, we will be able to offer any type of personalized medicine for people living with HIV (PLWH) and will be among the first companies worldwide to do so,” says Ahnfeld.

Text: Philipp Graf/Doreen Penso Dolfin

Featured image: © Catrin-Anja Eichinger

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