Developing Genetic Tools to Manipulate African Swine Fever Virus and Generate Attenuated Strains
African swine fever (ASF) is a devastating hemorrhagic disease of pigs with mortality rates up to 100% in infected pig herds. It is prevalent in many sub-Saharan African countries, causing major economic losses and threatening food security. Due to this sustained occurrence and the ever-increasing global traffic of people and goods, ASF poses an added global threat.
ASF is caused by a large DNA virus, African swine fever virus (ASFV), and there is currently no vaccine against it. A major roadblock has been the lack of convenient genetic tools to study this pathogen, with periods of up to a year of labor intensive effort just to generate one or two modified viruses, let alone to generate attenuated vaccine candidates.
In this study, through a collaboration between the J. Craig Venter Institute, the International Livestock Research Institute, and the Friedrich Loeffler Institute, we propose to leverage new synthetic biology tools, including CRISPR-Cas, to dramatically reduce the time to isolate mutant ASFV strains. In addition, by combining synthetic biology assembly methods with techniques to boot up infectious, we expect to develop a reverse genetics system for ASFV. The major effect of doing so will be the capacity to perform rapid and genome-wide modifications in ASFV and hence, significantly reduce the time to develop a variety of attenuated strains that can be tested as vaccine candidates.
Funding for this project provided by International Development Research Center Grant # 108514-001.