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A Synthetic Human Cytomegalovirus Vaccine Platform

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41AI106090-01A1
Agency Tracking Number: R41AI106090
Amount: $573,060.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NIAID
Solicitation Number: PA12-089
Solicitation Year: 2013
Award Year: 2013
Award Start Date (Proposal Award Date): N/A
Award End Date (Contract End Date): N/A
Small Business Information
505 NW 185TH AVE
BEAVERTON, OR 97006-3448
United States
DUNS: 968353347
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (301) 795-7254
Business Contact
Phone: (503) 341-1697
Research Institution
PORTLAND, OR 97239-3098
United States

 () -
 Nonprofit College or University

DESCRIPTION (provided by applicant): The goal of this project is to synthesize, based on genomic sequence information, a human cytomegalovirus (HCMV) strain with demonstrated ability to establish persistent infection in sero-positive individuals. The resulting synthetic product will form the basis for the development of attenuated HCMV vaccines. Innovative synthetic biology methods will overcome a shortcoming of current technologies that require extensive in vitro passaging of HCMV which often results in selecting tissue-culture adapted viral variants that are unlikely to be infectious. As proof-of-principle we will recreate the wild-ype version of the clinical isolate Toledo which has been used previously in clinical trials. Preliminay data suggest that early passages of Toledo contain a mixture of genomes displaying both tissue-culture adapted and non-adapted genotypes. We will determine the genomic sequence of the genotypes present in this mixture and use a combination of oligonucleotide synthesis, polymerase chain reaction, in vitro and in vivo assembly to recreate in a step-wise fashion a HCMV genome that will most closely resemble the original, wild-type sequence used in humans. The resulting virus, as well as spread-deficient variants, will be reconstituted in vitro and its growth characteristics will be compared to that of laboratory-adapted strains and other clinical isolates in vitro and in vivo using humanized NOD/SCID/IL2Rg-nul mice. If successful, this project would a) greatly facilitate the generation of molecular clones of CMV directly from sequence information without prior tissue culture, b) result in the largest viral genome synthesized to date, c) revolutionize the genetic manipulation of herpesviral genomes as well as that of other large DNAviruses. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: The development of vaccines against human cytomegalovirus (HCMV) and the use of HCMV as a vaccine carrier would be greatly facilitated by the availability of a HCMV strain with a provenability to persistently stimulate the immune system. In this project we will generate such an HCMV-strain using synthetic biology based on sequencing the genome of a low passage clinical isolate.

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

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