A synthetic genomics-based African swine fever virus engineering platform

Area of Science:

• Virology
• Genomics
• Veterinary Medicine

Background:

• African swine fever (ASF) is a highly contagious and deadly viral disease affecting domestic pigs globally.
• The economic impact on the swine industry is substantial, with the virus endemic in Africa, Europe, Asia, and Hispaniola.
• Current limitations in ASF control are due to the lack of effective treatments, vaccines, and tools for engineering the large ASFV genome.

Purpose of the Study:

• To develop a novel reverse genetics system for the African swine fever virus (ASFV).
• To overcome challenges associated with engineering the large, non-infectious ASFV genome.
• To facilitate the rapid generation of recombinant ASFV and combinatorial mutants.

Main Methods:

• Utilized synthetic genomics methodology to construct ASFV genomes.
• Employed a CRISPR-Cas9-inhibited self-helper virus system.
• Reconstituted infectious recombinant ASFV from synthetic DNA.

Main Results:

• Successfully established a functional reverse genetics system for ASFV.
• Demonstrated the ability to rapidly generate diverse ASFV mutants.
• The developed system overcomes previous limitations in ASFV genetic engineering.

Conclusions:

• The synthetic genomics approach provides a powerful tool for ASFV research and development.
• This methodology will significantly accelerate the creation of novel vaccines and therapeutics for ASF.
• The approach is adaptable for developing reverse genetics tools for other emerging viruses with large genomes.