After having claimed almost 33 million lives so far, there are currently 38M HIV-infected people worldwide and among them 2.5M residing in Europe. Lifelong antiretroviral therapy (ART) is generally well-tolerated and effective. However, due to considerable gaps in accessibility and compliance, an estimated 690K individuals have died from HIV related causes in 2019 and 1.7 million people were newly infected.
As an alternative to ART, broadly neutralizing antibodies (bNAbs) can also suppress the virus, but they may have to be chronically administered at an even higher cost. There thus remains a pressing need for a “one shot” HIV gene therapy. The goal of our project is to develop a one-shot treatment for HIV using “Switch targeting”: B cell engineering without nucleases, harnessing natural breaks to express desired anti-HIV bNAbs. In particular, we use viral vectors to target the integration of the bNAb gene into breaks that are naturally induced in activated B cells. Our design facilitates HIV-induced activation of engineered B cells, leading to differentiation into memory cells and antibody secreting plasma cells, as well as affinity maturation of the engineered antibody. Our technology, here demonstrated in mouse B cells, thus provides a single-shot functional cure of HIV. It includes unique safety features. It addresses viral variability between patients and it counteracts viral escape. Our technology will affect the lives of millions and will disrupt a $25B market.
