JAN BIOTECH, INC. — Department of Health and Human Services STTR Phase I: NIAID

Description

DESCRIPTION provided by applicant The CDC estimates that in the U S people aged years and older are living with HIV infection with approximately others infected but undiagnosed CDC Strict adherence to highly active combination anti retroviral therapy HAART cART prevents full blown AIDS However HAART cART fails to cure HIV infection as it has little effect on CD cells infected with latent forms of the virus If a patient no longer adheres to their prescribed regimen of HAART cART the latent pool quickly rebounds into full blown HIV infection Thus HIV AIDS is still far from eradicated Issues with Current Solutions andamp How Product Meets Unmet Needs Current methods of quantifying the latent reservoirs include the quantitative viral outgrowth assay Q VOA PCR and RT PCR Q VOA is accepted as the most accurate method but is a time and resource intensive procedure PCR grossly overestimates the latent pool through detection of unintegrated as well as nonfunctional virus DNA RT PCR can be used to detect viral RNA to virus particles per mL and thus reduces the time to result of QVOA and is generally applicable for measuring viral load but does not directly detect replication competent latent HIV infected cells Q VOA the accepted quantitation standard is currently available only at relativel few AIDS research facilities due to its intensive resource and labor requirements This product will introduce a real time molecular assay to detect transcriptionally competent HIV mRNA directly from latently infected cells isolated from HAART cART patients With validation against the Q VOA standard this assay has the potential to provide high throughput real time and lower cost quantitation of the latent HIV infected reservoirs in the body and significantly accelerate testing and discovery of a cure for HIV infection Summary of Approach The product proposed is a real time quantitative autoligation detection reaction qLDR which uses fluorogenic probes for chemical ligation in a thermocycling amplification reaction qLDR allows for real time and accurate quantification of the level of HIV mRNA present in CD latent HIV infected cells The proposed assay will employ modified fluorogenic nucleic acid probes for superior stability and highly specific HIV RNA detection for quantifying latent HIV infected reservoirs Collaborators and Unique Resources Jan Biotech Inc with expertise in molecular diagnostic development will collaborate with Dr David Putnam a chemist in the Department of Chemical and Biomolecular Engineering of Cornell University Dr Harris Gelbard investigating the phenomenon of latent reservoir induced neuroAIDS at the University of Rochester Center for AIDS Research CFAR and CFAR will provide consultation and HAART cART CD samples Cell lines will be provided by the NIH AIDS Reagent Program Q VOA validation testing will be performed by CARE Phase I Specific Aims Specific Aim Develop spliced RNA detection assay for quantitation of latent HIV infected cells Specific Aim Test qLDR with HAART patient CD cells and validate against Q VOA How Anticipated Results will Justify Phase II and Further Product Development Superior performance of qLDR is expected compared to Q VOA and Q VOA with RT PCR with real time sensitive and specific detection of spliced HIV mRNA directly from latent HIV infected CD cells from HAART cART patients Successful Phase I validation against the Q VOA standard will justify Phase II full validation and product development to produce a high throughput commercial ready laboratory research assay platform Additional Time and Funding Necessary to Bring Product to Market after Phase I Completion It is anticipated that a high throughput laboratory research product can be brought to market as a laboratory assay kit for research purposes at the completion of the Phase II two years after the Phase I work has been completed It is anticipated that an additional years and funding through a Phase II bridge award will be needed to perform the clinical trials required for FDA approval as a clinical diagnostic PUBLIC HEALTH RELEVANCE The CDC estimates that in the U S people aged years and older are living with HIV infection with approximately others who are infected but undiagnosed CDC Highly active anti retroviral therapy HAART combination anti retroviral therapy cART while keeping HIV infection in remission fails to eradicate reservoirs of latent HIV infected cells in patients Strategies targeting this latent reservoir are now being tested in clinical trials and well validated high throughput assays that quantify this reservoir are urgently needed to facilitate the complete eradication of HIV AIDS