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NOVEL DRUGS FROM UNCULTURABLE FUNGI

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: AI40799-01
Agency Tracking Number: 39338
Amount: $99,900.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: N/A
Solicitation Number: N/A
Timeline
Solicitation Year: N/A
Award Year: 1997
Award Start Date (Proposal Award Date): N/A
Award End Date (Contract End Date): N/A
Small Business Information
1 KENDALL SQUARE, BLDG 300
Cambridge, MA 02139
United States
DUNS: N/A
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 AN, ZHIQIANG
 () -
Business Contact
Phone: (617) 374-9090
Research Institution
N/A
Abstract

There is an urgent need for new therapeutic drugs in many therapeutic areas. Millennium Pharmaceuticals was established to meet these challenges using fungal secondary metabolites as a major drug source. Traditionally, fungi that have been selected for drug screening are those that can be easily cultured in the laboratory; however, culturable fungi constitute only a fraction of the fungal taxa. In this project, we propose to develop a novel technology to capture the genetic diversity from unculturable fungi through genetic engineering. We will clone large segments of genomic DNA from selected unculturable fungi and introduce the cloned DNA into closely related, genetically amenable laboratory strain to express genes from the unculturable fungi and to produce novel secondary metabolites with biological activities. $ = TOTAL AWARD AMTS & NOT LIMITED TO PORTION OF PROJECT RELATED TO SUBJECT OF SEARCH SUBPROJECT $ = TOTAL AWARD AMOUNT DIVIDED BY NUMBER OF SUBPROJECTS SOURCE: CRISP FORMAT F FY 97 LAST UPDATE 04-07-98 1QUERY 1536 ID SEARCH 06/01/98 PAGE 71 --PROJECT NUMBER......1 R43 AI40802-01A1 INVESTIGATOR NAME/ADDRESS FY 97 JAYNES, JESSE M IRG/INTRAMURAL UNIT..ZRG5 DEMETER BIOTECHNOLOGIES, LTD AWARD AMOUNT......... $100,000 905 WEST MAIN STREET, SUITE 19 DURHAM, NC 27701 PERFORMING ORGANIZATION: DEMETER BIOTECHNOLOGIES, LTD. TITLE INTERRUPTION OF STD TRANSMISSION WITH PEPTIDYL MIMSTM ABSTRACT: DESCRIPTION (Adapted from the Applicant's Abstract): The increasing incidence of sexually transmitted diseases (STDs) and women's needs to protect their reproductive health are impetus for development of novel methods of STD prophylaxis. Peptidyl Membrane Interactive Molecules (Peptidyl MIMsTM) from Demeter BioTechnologies, Ltd. are unique peptide antibiotics that kill STD pathogens in vitro at low concentration, while demonstrating minimal intravaginal irritation or systemic toxicity in animal models. Phase I studies will develop gel formulations for intravaginal administration with Demeter's two lead anti-STD compounds. Formulated gels will be tested against gonorrhea and trichomoniasis in in vitro assays. These microbicides will then be tested intravaginally in murine animal models to determine their ability to interrupt gonorrhea and trichomoniasis transmission, without causing significant irritation or toxicity within the vagina. Histopathologic examinations will be conducted to determine local and systemic effects of drugs and disease progress in the animal models. Upon demonstration of significant reduction in STD transmission in the animal models, Phase II studies will be sought to conduct the necessary tests to apply for an Investigational New Drug with the United States Food and Drug Administration (FDA). Human clinical studies would follow. $ = TOTAL AWARD AMTS & NOT LIMITED TO PORTION OF PROJECT RELATED TO SUBJECT OF SEARCH SUBPROJECT $ = TOTAL AWARD AMOUNT DIVIDED BY NUMBER OF SUBPROJECTS SOURCE: CRISP FORMAT F FY 97 LAST UPDATE 04-07-98 1QUERY 1536 ID SEARCH 06/01/98 PAGE 72 --PROJECT NUMBER......1 R43 AI40821-01 INVESTIGATOR NAME/ADDRESS FY 97 NERI, BRUCE P IRG/INTRAMURAL UNIT..ZRG5 THIRD WAVE TECHNOLOGIES INC AWARD AMOUNT......... $85,308 2800 S FISH HATCHERY RD MADISON, WI 53711 PERFORMING ORGANIZATION: THIRD WAVE TECHNOLOGIES TITLE DETECTION OF RIFAMPIN RESISTANT M TUBERCULOSIS ABSTRACT: For the past three decades, Mycobacterium tuberculosis infections have declined in the United States, and it was thought that the disease would be virtually eliminated by the year 2000. However, the trend was reversed in 1985, and, as of 1992, an estimated 51,700 cases in excess of the 1984 projections have occurred in the United States (41). Even more disturbing has been the commensurate rise in the isolation of M. tuberculosis strains resistant to one or more of the antibiotics commonly used to treat the infection. While rapid detection methods based on nucleic acid amplification technologies have offered the promise of early detection of M. tuberculosis infection, to control this resurgent health problem these new diagnostic methods must be complemented by rapid tests for determining effective antibiotic therapy. The mechanisms of resistance to several of the front line drugs in M. tuberculosis have been identified and shown to be the result of mutations in key genes. In particular reports indicate that more than 95% of M. tuberculosis isolates exhibiting resistance to rifampin harbor specific mutations within a 69-bp region of the rpoB gene, which encodes the beta subunit of RNA polymerase. An opportunity exists, therefore, to create a diagnostic procedure based on the rapid detection of these genetic changes which lead to drug resistance. Because of these observations that genetic mutations play a significant role in the development of drug resistance in M. tuberculosis, methods which rapidly detect such mutations may play an important role in the clinical management of patients with tuberculosis. In this Phase I proposal, we will develop a model system for rapidly detecting mutations which lead to rifampin-resistance in M. tuberculosis using our proprietary Cleavase(R) Fragment Length Polymorphism (CFLPTM) technology. This work will form the foundation of genetic-based diagnostic tests for drug resistance in M. tuberculosis all of which will be based on our rapid, cost effective, and highly accurate CFLPTM technology.

* Information listed above is at the time of submission. *

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