Wigdahl directs the Institute for Molecular Medicine and Infectious Disease and chairs the Department of Microbiology & Immunology in the College of Medicine.
Nonnemacher is a professor in the Department of Microbiology & Immunology.
Dampier is an assistant professor in the College of Medicine.
Researchers in the College of Medicine are advancing a multi-institutional, NIH-funded effort to use CRISPR gene-editing technology to cure HIV.
A cure for HIV would improve and extend the lives of some 38 million infected people worldwide. While existing antiviral therapies suppress HIV effectively, they must be taken daily for the duration of a patient’s life, carrying long-term toxicity, cost and stigma.
Three faculty members — Brian Wigdahl, Michael Nonnemacher and Will Dampier — are developing a treatment that targets a large swath of HIV virus strains known as quasi–species, using CRISPR/Cas9.
CRISPR uses a protein called Cas9 and a guide RNA (gRNA) to target the HIV “hiding” in host DNA. The researchers have found a way to target sequences in the HIV provirus located in the chromosomes of infected cells and then produce irreversible edits that prevent virus replication or eliminate the virus from the cell altogether.
By removing the virus from the host cell, Dampier says, “CRISPR fits into a cure strategy niche that no other treatment can fulfill.”
“CRISPR fits into a cure strategy niche that no other treatment can fulfill”
By targeting the viral quasispecies present in people living with HIV, the treatment could help a broad spectrum of individuals. Dampier and Nonnemacher spearheaded a group who devised an algorithm to identify gRNAs with the greatest potential to work with CRISPR. To design the algorithm, they gleaned gene-sequencing data from individuals treated through the Partnership Comprehensive Care Practice that the College of Medicine established in 1993 to serve Philadelphia residents.
The trio are among a “supergroup” — including investigators at Temple University and other academic institutions, a research institute, and a biotech company developing the CRISPR for Cure project — that has been awarded $4.8 million annually for five years from the National Institutes of Health.
It may take a combination of therapeutic strategies to achieve a “cure,” Wigdahl says, explaining that effective cell and gene therapies may be needed to enhance HIV immune control mechanisms and eliminate the viral genome from infected cells, in addition to vehicles that can deliver therapies to the tissue and circulating cell reservoirs where the virus hides.