R01AI158160

Laser Art for Prep - Abstract

This project contains a highly collaborative investigative team with interdisciplinary expertise, with significant potential impact for HIV/AIDS prevention. The proposal includes pharmacologic, virologic, animal, and product development studies designed to halt disease transmission through novel long-acting (LA) antiretrovirals. These are named LA Slow Effective Release Antiretroviral Therapies (LASER ART), designed to facilitate HIV-1 prevention by intense bench to the clinic translational studies.

Innovative interdisciplinary approaches contain a detailed research plan, extensive preliminary, and broadly published supportive data. Creativity and innovativeness are offered, placed at higher risk than a conventional research project. The work builds on the development of parenteral nanoformulations of chemically modified antiretroviral drugs designed to improve adherence. The drugs are currently offered once a day in pill form but will be converted to up to once a year administration.

Support from expert pharmacologists and pharmaceutical scientists with university researchers are operative. The drugs include Dolutegravir (DTG), Emtricitabine (FTC), and Tenofovir (TFV) created to extend their apparent drug half-life, efficacy, and abilities to target viral reservoirs. They are, in measure, DTG and FTC and TFV prodrug + nucleotide (protides) designated "N" for nanoformulation, "M" for esterification, and "P" for protides.

The created NPFTC and NPTFV and NM2DTG demonstrate sustained plasma and tissue drug concentrations of > 90% inhibitory concentration from months to a year. Based on encouraging results, we seek funds to facilitate large-scale development that would facilitate future human studies. The final formulations would be characterized by sustained prodrug hydrolysis with reduced injection volumes.

The pathway forward follows an established partnership with the Clinton Health Access Initiative and oversight by Viiv Healthcare and Gilead Sciences. The overarching goal is safety, reproducibility, and "scale-up" that follows US Food and Drug Administration-approved current good manufacturing practices (CGMP). The specific aims are each supported by extensive published data sets forged through the multidisciplinary research.

Creation and characterization focus on prodrug formulations, toxicology, and pharmacokinetics profiles following a safe developmental action plan. The work is facilitated by a fully operational CGMP facility and rhesus macaque validations. The lead formulation will be developed with our CHAI partners. We posit that the creation of LASER ART DTG or FTC and TFV will have a profound impact on HIV prevention.

Board Of Regents Of The University Of Nebraska

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.

93.855 - Allergy and Infectious Diseases Research

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

Omaha, Nebraska 681987835 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 393% from $710,244 to $3,504,782.