Provirex is pioneering a groundbreaking approach to HIV treatment that diverges significantly from the established antiretroviral therapies. While conventional medications focus on suppressing viral replication, they leave behind HIV DNA, known as proviruses, embedded within the genomes of long-lived immune cells. Provirex aims to eliminate these viral DNA sequences from the genetic material of infected cells using an innovative genome-editing method. If successful, this could drastically reduce the number of HIV-infected cells over time, potentially leading to the eradication of the viral reservoir—the key requirement for achieving a functional or complete cure of the infection.
Addressing the Root of the Problem
The objective of Provirex’s approach is not merely to suppress viral replication but to eradicate the actual HIV reservoir. HIV integrates its genetic material into the genomes of long-lived immune cells, evading even decades of antiretroviral treatment. The company utilizes a designer recombinase, Brec1, which has been artificially developed in the laboratory of Frank Buchholz at TU Dresden. This recombinase targets a conserved DNA sequence that is shared by over 90% of known HIV variants. By excising the fully integrated viral segment from the chromosome, Brec1 reconnects the ends of human DNA.
Unlike CRISPR technology, which cuts DNA and relies on the cell’s repair mechanisms, Provirex’s recombinase takes on both the cutting and rejoining of DNA itself. This offers a critical safety advantage, as there is no persistent double-strand break in the DNA that could lead to errors during repair.
Clinical Trials on the Horizon
Currently, Provirex’s clinical strategy is based on an ex vivo approach. Blood-forming stem cells—or specifically infected CD4 T-cells—are extracted from the patient, engineered to carry the Brec1 gene, and subsequently reinfused. The company is developing patient-specific cell therapies whereby T-cells are genetically modified outside the body and then reintroduced into the patient. Their infrastructure, consolidated in Hamburg’s Tech-Park, aims to cover the entire value chain from research to quality control and subsequent GMP production. Presently, Provirex employs 19 staff members and has recently filled key positions in manufacturing, quality control, and assurance, while preparing for GMP certification of its facility.
This marks a significant improvement over their initial foray into clinical testing shortly after the company was founded in 2019. As commented by CEO Dr. Jan-Uwe Claas-von Jachmann, poor selection of study centers and the company’s passive role contributed to severe delays and eventual discontinuation of initial efforts. Now, however, they possess full control over production processes and are well-positioned with various university hospitals in Frankfurt, Essen, Düsseldorf, Cologne, and LMU Munich to initiate the clinical proof-of-concept phase with eight patients in the coming year.
The Global Landscape: A Narrowing Focus
Currently, only the U.S.-based company Excision BioTherapeutics is working on strategies to eliminate latent HIV reservoirs, employing CRISPR technology. However, initial studies have not yielded clinical proof of a lasting cure. The rise of HIV infections continues to be a pressing issue, particularly as the perception grows that HIV/AIDS is now manageable with current treatments. Continuous use of therapeutic drugs is essential for effective control, meaning lifelong adherence is necessary. Any discontinuation leads to rapid viral re-emergence.
Secured Funding and Promising Clinical Data
Provirex has secured sufficient funding from the Hamburg Investment and Development Bank (IFB), Bioventure, Ascenion, and various individual investors to support its clinical studies. They anticipate that upcoming clinical data will substantiate the virus elimination observed in infected mouse models will also translate to human subjects. This success could potentially renew interest in gene therapy approaches across other chronic diseases.
Moving forward, Provirex is also exploring in-vivo administration, aiming to deliver the recombinase directly into infected cells within the body. By utilizing nanobody-decorated lipid nanoparticles as carriers for the Brec1 gene, they envision a broader application of this technology, potentially transforming the landscape of HIV treatment.
