Combinatorial Approaches to Viral Attenuation
Abstract
Live viral vaccines rely on attenuated viruses that can successfully infect their host but have reduced fitness or virulence. Such attenuated viruses were originally developed through trial and error, typically by adaptation of the wild-type virus to novel conditions. That method was haphazard, with no way of controlling the degree of attenuation or the number of attenuating mutations or preventing evolutionary reversion. Synthetic biology now enables rational design and engineering of viral attenuation, but rational design must be informed by biological principles to achieve stable, quantitative attenuation. This work shows that in a model system for viral attenuation, bacteriophage T7, attenuation can be obtained from rational design principles, and multiple different attenuation approaches can be combined for enhanced overall effect.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Aug 28, 2018
- Source ID
- 10.1128/msystems.00046-18
Entities
People
- Bartram L. Smith
- Benjamin R Jack
- Claus O. Wilke
- James J. Bull
- Matthew L. Paff
Organizations
- Army Research Office
- National Institutes of Health
- National Science Foundation of Sri Lanka
- University of Texas at Austin