A therapeutic trial using innovative CRISPR-based technologies to target the African swine fever virus (ASFV) in pigs has successfully been completed, Seek Labs announced on May 6. The trial, which aimed to replicate and expand an earlier trial, demonstrated pigs infected with ASFV and treated with Seek Labs’ CRISPR-based systems survived longer than untreated infected pigs, the company said in a release.
“Over half of the CRISPR-treated pigs survived beyond the duration of the trial. Observations and data from both studies reveal compelling outcomes where treatment prolonged lifespans of infected pigs compared to control groups,” the release noted.
Seek Labs is developing CRISPR-based systems that selectively target pathogenic diseases, including viral infections. What does this mean? This approach disrupts viral replication, slows progress of an infection, and allows treated animals to mount an immune response that can lead to extended survival and even potentially achieve curative outcomes, the company explained.
“I have worked on developing vaccine candidates for African Swine Fever for over 15 years. With no available treatments for African Swine Fever, this is a breakthrough discovery. These are excellent results that indicate the potential to dramatically increase survivability in pigs against ASFV infection and treat other animal diseases,” Doug Gladue, PhD, an internationally recognized leader in ASFV research and vaccine development, said in a release.
Seek Labs pointed out the potential of CRISPR to tackle infectious diseases across species in the release. The company initially demonstrated their CRISPR-based systems reduce viral load in vivo using a Litopenaeus vannamei shrimp model infected with White Spot Syndrome Virus (WSSV). These proof-of-concept studies consistently achieved approximately 80% reduction in viral load as validated by qPCR. This outcome correlated with moderate extension in survival times for CRISPR-treated infected shrimp relative to untreated infected shrimp and prompted further anti-viral testing of the CRISPR technology platform.
To expand evaluation of the CRISPR-based systems, Seek Labs studied anti-viral modalities in pigs infected with ASFV. The company launched independent in vivo trials in a region overseas where ASF is currently endemic in domestic swine.
“CRISPR is a highly adaptable gene targeting technology that holds enormous potential as a therapeutic modality across genomes,” Alison O’Mahony, vice president of pharmaceutical research at Seek Labs, said in the release. “Our CRISPR platform leverages Cas systems and multiplexed gRNAs to selectively target pathogenic genomes.”
Seek Labs is currently advancing two CRISPR-based systems with multiplexed ASFV-targeting gRNAs for in vivo testing. Both ASFV-targeting candidates were administered to infected pigs via intramuscular injections either as a single dose on one day or as a double dose on two consecutive days, the release said. All pigs were monitored for four weeks for the appearance of infection-related symptoms. Pigs were weighed and blood was drawn and tested for the presence of an ASF virus gene using qPCR, as well as for anti-ASFV antibodies by ELISA assays.
The trial demonstrated the CRISPR candidates prolonged survival in ASFV-infected pigs treated with candidates and achieved curative outcomes in a subset of the treated pigs.
“Data show 57% of the CRISPR-treated cohorts survived longer than the control cohort. Not only did the CRISPR-treated cohort survive beyond the end of the trial, but this cohort was observed to be consistently more physically active and responsive to stimuli throughout the trial. Data also indicate CRISPR targeting of the ASFV genome decreased viral load. Taken together, these data suggest ASFV did not lead to a lethal infection in multiple CRISPR-treated pigs,” the release said.
All surviving pigs are being tested for protection against reinfection at this time. Future studies will also look at efficacy outcomes following prophylactic versus therapeutic delivery of the CRISPR-based systems. The company is considering applications in new viral outbreaks, including ongoing Avian Influenza (H5N1) outbreaks that have already transmitted from chickens to cows and impacted food supply in the U.S., the article said.
