UM1AI164567

Collaboratory of AIDS Researchers for Eradication (CARE) - Abstract

Since its inception in 2011, the Martin Delaney Collaboratory Program has made important advances towards a cure for HIV. In response to the Martin Delaney Collaboratories (MDC) for HIV Cure Research RFA, we seek to continue to advance the field by discovery of successful modalities to cure HIV infection.

We will expand our expertise and work toward a better understanding of persistent HIV infection, the discovery of novel approaches to disrupt latency, methods to clear the HIV reservoir, and identification of strategies to control viral rebound. By building on the significant advances that we have made to develop, implement, and execute a suite of pre-clinical experiments that represent the most advanced and novel concepts, we will continue to pursue our central unifying hypothesis that reversing HIV latency such that viral proteins are expressed, in parallel with interventions that speed the clearance of cells emerging from latent infection, will ultimately lead to eradication of persistent HIV infection.

In parallel to the efforts to clear the infection, we will pursue interventions to prevent rebound of viremia after ART interruption. We will leverage a broad portfolio of tools from both academic and industry partners and apply new discoveries, demonstrating proof-of-concept for clinical initiatives. We will engage academic scientists and clinicians, industry investigators, and the community to:

A) Define novel targets to destabilize proviral genomes that persist despite antiretroviral therapy (ART)
B) Define novel approaches to block proviral establishment
C) Develop and deploy novel effectors to clear viral reservoirs
D) Delineate effective strategies to prevent rebound viremia that might emanate from such reservoirs after ART is discontinued
E) Create bridges to the community to improve the understanding of and access to HIV cure research and clinical trials.

Our initial efforts will focus on biology discovery to illuminate new host targets for latency reversal and the validation of the novel biological concept of latency prevention. Universal strategies for proviral control or clearance will be developed and tested, including those based on HLA-E targeting, ECD4, and CD4 mimetics. Our major recent advance in latency reversal via NF-KB signaling will be further developed in both non-human primate and humanized mice models, in combination with candidates to clear infected cells.

We envision an iterative process with insights gained in ex vivo and pre-clinical studies, carried forward to enhance the next step in clinical development and, importantly, fed back to scientists to validate assays or hypotheses and explore new directions. As we have done in the past, we will develop human clinical trials to address questions and test concepts developed in our work through funding mechanisms distinct from CARE.

We are dedicated to working together in a nimble program, with our research direction following our discoveries. Together, we will catalyze advances that will ultimately lead to the eradication of HIV infection.

University Of North Carolina At Chapel Hill

TO ASSIST PUBLIC AND PRIVATE NONPROFIT INSTITUTIONS AND INDIVIDUALS TO ESTABLISH, EXPAND AND IMPROVE BIOMEDICAL RESEARCH AND RESEARCH TRAINING IN INFECTIOUS DISEASES AND RELATED AREAS, TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS. TO ASSIST PUBLIC, PRIVATE AND COMMERCIAL INSTITUTIONS TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS, TO PROVIDE RESEARCH SERVICES AS REQUIRED BY THE AGENCY FOR PROGRAMS IN INFECTIOUS DISEASES, AND CONTROLLING DISEASE CAUSED BY INFECTIOUS OR PARASITIC AGENTS, ALLERGIC AND IMMUNOLOGIC DISEASES AND RELATED AREAS. PROJECTS RANGE FROM STUDIES OF MICROBIAL PHYSIOLOGY AND ANTIGENIC STRUCTURE TO COLLABORATIVE TRIALS OF EXPERIMENTAL DRUGS AND VACCINES, MECHANISMS OF RESISTANCE TO ANTIBIOTICS AS WELL AS RESEARCH DEALING WITH EPIDEMIOLOGICAL OBSERVATIONS IN HOSPITALIZED PATIENTS OR COMMUNITY POPULATIONS AND PROGRESS IN ALLERGIC AND IMMUNOLOGIC DISEASES. BECAUSE OF THIS DUAL FOCUS, THE PROGRAM ENCOMPASSES BOTH BASIC RESEARCH AND CLINICAL RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM EXPANDS AND IMPROVES PRIVATE SECTOR PARTICIPATION IN BIOMEDICAL RESEARCH. THE SBIR PROGRAM INTENDS TO INCREASE AND FACILITATE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATES AND FOSTERS SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. RESEARCH CAREER DEVELOPMENT AWARDS SUPPORT THE DEVELOPMENT OF SCIENTISTS DURING THE FORMATIVE STAGES OF THEIR CAREERS. INDIVIDUAL NATIONAL RESEARCH SERVICE AWARDS (NRSAS) ARE MADE DIRECTLY TO APPROVE APPLICANTS FOR RESEARCH TRAINING IN SPECIFIED BIOMEDICAL SHORTAGE AREAS. IN ADDITION, INSTITUTIONAL NATIONAL RESEARCH SERVICE AWARDS ARE MADE TO ENABLE INSTITUTIONS TO SELECT AND MAKE AWARDS TO INDIVIDUALS TO RECEIVE TRAINING UNDER THE AEGIS OF THEIR INSTITUTIONAL PROGRAM.

93.847 - Diabetes, Digestive, and Kidney Diseases Extramural Research

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [HHS - NIH]

Chapel Hill, North Carolina 27599 United States

Single Zip Code

Martin Delaney Collaboratories for HIV Cure Research (UM1 Clinical Trial Not Allowed) (RFA-AI-20-035)

Amendment Since initial award the total obligations have increased 473% from $4,580,169 to $26,234,170.