HOST RANGE DIVERSITY OF BACTERIOPHAGE FOR Y. PESTIS

Award Information
Agency:
Department of Health and Human Services
Branch:
N/A
Amount:
$494,982.00
Award Year:
2006
Program:
SBIR
Phase:
Phase I
Contract:
1R43AI066449-01A1
Agency Tracking Number:
AI066449
Solicitation Year:
2006
Solicitation Topic Code:
N/A
Solicitation Number:
PHS2006-2
Small Business Information
AVIDBIOTICS CORPORATION
AVIDBIOTICS CORPORATION, 385 Oyster Point Blvd., Suite 6A, SOUTH SAN FRANCISCO, CA, 94080
Hubzone Owned:
N
Socially and Economically Disadvantaged:
N
Woman Owned:
N
Duns:
N/A
Principal Investigator
 DAVID MARTIN
 (415) 421-3588
 dmartin@avidbiotics.com
Business Contact
Phone: (650) 873-1101
Research Institution
N/A
Abstract
DESCRIPTION (provided by applicant): Yersinia pestis, the bacterium responsible for plague, is a Category A pathogen, a significant biowarfare agent. If weaponized, it can easily gain direct access to the respiratory system to cause rapid death by pneumonic plague. Pneumonic plague has fatality rates over 50%, is highly contagious, and if the bacteria are engineered to resist antibiotics, is essentially unbeatable. As a countermeasure to such a threat, we propose to develop a library of bacteriophages ("phages") specific for Y. pestis that can kill multiple strains of this bacterium in a highly efficient manner. AvidBiotics has exclusive access to technology to generate families of phage with highly diverse tails capable of binding to mutant forms of bacteria, such as Bordetella. In this application, we propose to develop a library of phage to bind to, infect and kill mutant Y. pestis bacteria, anticipating potential mutations engineered into the bacteria to change their sensitivities to antibiotics or surface receptors for phage. This technology is based on the discovery of a family of diversity-generating retroelements (DGRs) that function to vary DNA sequences and the proteins they encode. These DGRs can be engineered into phages to diversify specifically the amino acid sequence of the precise receptor-binding site of the phage tail fiber, thereby generating a library of phages with more than a trillion different possible tails targeting Y. pestis cell surface receptors. By exposing such a phage library to mutant or weaponized plague bacteria, phages capable of infecting, multiplying and killing the bacteria could be identified, selected, isolated, amplified, aerosolized and then deployed to protect against or treat infections by weaponized Y. pestis. The objective of this application is to demonstrate the ability to utilize the DGR-system to precisely and extensively diversify the phage tail fiber sequences as a means to create novel phage with broad Y. pestis tropism. These studies will provide the foundation for future studies to generate a suitable, formulated pool of highly diverse phages that will serve as a reliable, productive source of diagnostic and therapeutic agents effective against weaponized plague bacteria. We anticipate that a Phase II follow-on project would entail developing a process to GLP manufacture and formulate representative members of the diverse phage library targeting Y. pestis and conduct pre-clinical safety studies to prepare a rapid response counter- terrorism system to manage pneumonic plague in humans.

* information listed above is at the time of submission.

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