The First CRISPR-Based Therapeutic (SL_1.52) for African Swine Fever Is Effective in Swine

Area of Science:

• Veterinary Virology
• Molecular Biology
• Gene Editing Therapeutics

Background:

• African swine fever virus (ASFV) causes African swine fever (ASF), a highly contagious disease with 90-100% mortality in pigs.
• Current ASF control relies on culling, with limited, strain-specific vaccines available only in limited regions.
• CRISPR/Cas systems offer programmable, sequence-specific targeting for therapeutic applications.

Purpose of the Study:

• To develop and evaluate a CRISPR/Cas9-based therapeutic strategy against African swine fever virus (ASFV).
• To demonstrate the efficacy of targeting the ASFV genome using a multiplexed guide RNA (gRNA) system.
• To assess the impact of CRISPR/Cas9 treatment on viral load, animal survival, and subsequent immunity.

Main Methods:

• Design and implementation of a multiplexed CRISPR/Cas9 system with guide RNAs (gRNAs) specific to the ASFV genome.
• In vivo administration of the CRISPR/Cas9 system to ASFV-infected pigs.
• Monitoring of viral load, clinical signs, survival rates, and challenge with homologous ASFV post-recovery.

Main Results:

• Demonstrated sequence-specific cleavage of the ASFV genome by the CRISPR/Cas9 system.
• Significant reduction in viral load in ASFV-infected animals treated with the CRISPR/Cas9 therapy.
• Successful recovery from a lethal ASFV dose and development of protective immunity against homologous ASFV challenge.

Conclusions:

• CRISPR/Cas9 gene editing represents a promising novel therapeutic modality for African swine fever.
• This approach offers a potential strategy for reducing viral load and improving outcomes in ASF-infected animals.
• The study highlights the potential for CRISPR technology in combating viral pandemics in livestock.