The mission of the HOPE Collaboratory is to find a cure for HIV using a novel “block-lock-excise” approach—that entails the long-term durable silencing of viral expression towards permanent excision of the latent virus and control of virus infection in the absence of therapy. Our goal is to turn PLWH into PLWOH, people living without HIV. This is achieved through a graded transformation of remnant HIV in PLWH from latent to silent into permanently defective proviruses, thus emulating and accelerating the natural path that endogenous retroviruses have taken in the human genome over millions of years. After silencing, we propose a final coup de grace: excision of remnant virus for permanent cure.

Why is the HOPE approach significant?

We expect to contribute transformative detailed information and radically new therapeutic approaches to turn PLWH into PLWOH.
We expect to provide novel silencing compounds and innovative gene-engineering methodologies
to support both “functional” and “classical” cure approaches.

HOPE is organized into the three Research Foci to achieve these goals.

Research Focus 1 will explore the HIV promoter architecture and occupancy at the basic level and takes advantage of lessons learned from the way our cells efficiently silenced HERVs.

Research Focus 2 will examine viral rebound after treatment with silencing promoting agents (SPAs) that are clinically approved and will also screen for new SPAs. Additionally, novel sequence-specific silencing approaches will be explored for HIV.

Research Focus 3 will work towards eradication of the HIV virus by developing and optimizing genome-engineering approaches for safe and permanent mutation or excision of the virus. This includes research into efficient targeted delivery methods.