Seek Labs, a health care innovations company developing next-generation point-of-care molecular diagnostic systems and novel CRISPR-based gene therapies, has successfully completed a therapeutic trial using innovative CRISPR-based technologies to target the African swine fever virus (ASFV) in pigs.
The trial, which aimed to replicate and expand a previous trial, demonstrated pigs infected with ASFV and treated with Seek Labs’ CRISPR-based systems survived longer than untreated infected pigs. 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 with control groups.
Innovative CRISPR-based treatment approach
Seek Labs is developing CRISPR-based systems that selectively target pathogenic diseases, including viral infections. 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.
“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,” said Dr. Doug Gladue, Ph.D., an internationally recognized leader in ASFV research and vaccine development. “These are excellent results that indicate the potential to dramatically increase survivability in pigs against ASFV infection and treat other animal diseases.”
Seek Labs recognizes the potential of CRISPR to tackle infectious diseases across species. 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.
Seek Labs expanded evaluation of the CRISPR-based systems as antiviral modalities in pigs infected with ASFV. To this end, the company launched independent in vivo trials. Due to strict regulations in the United States that limit African swine fever (ASF) research, Seek Labs conducted the trials overseas in a region where ASF is endemic in domestic swine.
“CRISPR is a highly adaptable gene-targeting technology that holds enormous potential as a therapeutic modality across genomes,” said Alison O’Mahony, vice president of pharmaceutical research at Seek Labs. “Our CRISPR platform leverages Cas systems and multiplexed gRNAs to selectively target pathogenic genomes.”
In vivo ASFV trial design
Seek Labs is advancing two CRISPR-based systems with multiplexed ASFV-targeting gRNAs for in vivo testing: Candidate SL_1.52, which comprises a single Cas-encoding construct, and Candidate SL_1.52/SL_1.45 Combo, which comprises a combination of two Cas-encoding constructs.
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. All pigs were monitored daily for four weeks for the appearance of infection-related symptoms. Per the study protocol, 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.
Trial outcomes
The trial demonstrated Seek Labs’ 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.
Future research and studies
All surviving pigs are now being tested for protection against reinfection. 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 United States.
Seek Labs will continue pursuing innovative gene editing technologies to expand antiviral and disease treatment strategies.