African swine fever virus (ASFV), a lethal disease-causing staggering losses in the global pork industry, is notoriously tricky to study. Now, a team from the J. Craig Venter Institute (JCVI), the Friedrich-Loeffler-Institut (FLI), and the International Livestock Research Institute (ILRI) has built a cutting-edge reverse genetics system poised to transform ASFV research and prevention efforts. Detailed in a recent issue of Science Advances, this synthetic genomics-based tool allows scientists to engineer genetically modified ASF viruses rapidly—an innovation that could reshape the fight against viral diseases.

ASFV, highly contagious among domesticated and wild pigs, remains rampant across Africa, Europe, Asia, and the Caribbean. A recent report warned that a U.S. outbreak could cost over $50 billion in economic losses within a decade. "Globally, ASF outbreaks have caused devastating economic losses amounting to billions of dollars, severely impacting the pork industry, food security, and livelihoods," said ILRI researcher and study author Dr. Hussein Abkallo. In Africa, multiple ASFV strains and insufficient biosecurity exacerbate the challenge. “This platform gives hope of developing new, targeted vaccines that can protect animal health, reduce mortality, and minimize environmental footprints,” Abkallo emphasized.

Synthetic DNA and CRISPR: Inside the Cutting-Edge ASFV Platform

At the heart of this innovation lies synthetic genomics, a field dedicated to constructing artificial DNA sequences. Scientists first engineer synthetic fragments of ASFV’s genome in the laboratory, modifying genetic elements to investigate the virus or elicit specific immune responses. These fragments are then recombined into full-length ASFV genomes using yeast’s natural genetic recombination machinery. To scale this work, the newly assembled genomes are transferred into E. coli bacteria, simplifying genome isolation and amplification.

The next step involves introducing this synthesized DNA into mammalian host cells—a process known as transfection—where it meets a specialized "self-helper" virus. Modified via CRISPR/Cas9, this self-helper virus is an ASFV variant rendered incapable of independent replication but still capable of producing essential proteins required by the synthetic genome. With its help, synthetic DNA replicates successfully, forming new virus particles that can be studied or utilized in vaccine development.

JCVI senior author Professor Sanjay Vashee highlighted this advancement's broader implications: “By developing a synthetic genomics-based reverse genetics system for ASFV, we are not only advancing our understanding of this virus but also creating tools applicable to other emerging viral threats.” This approach holds promise beyond ASFV, providing a pathway to rapidly respond to other viral pathogens.

From ASFV to Ebola: Expanding the Viral Toolkit

Indeed, the technology’s versatility extends well beyond swine fever. Viruses such as lumpy skin disease virus—which severely impacts cattle—could soon be targeted using similar synthetic genomics platforms. Likewise, researchers envision the tool's application in managing dangerous RNA viruses, including Zika, chikungunya, Mayaro, and Ebola—agents responsible for devastating outbreaks globally.

As JCVI’s Vashee points out, synthetic genomics enables researchers to swiftly respond to novel threats, facilitating in-depth study of virus biology, enhancing preparedness, and accelerating vaccine development. With the capacity to confront ASFV and a host of other deadly viruses, synthetic genomics stands poised as a cornerstone technology in global disease control and prevention.