- Manipulating genetic variation in Coronary Artery Disease (CAD)
Several genetic variations (SNPs) have been recently associated with an increased risk of CAD. We are engineering zinc finger, TALE, and CRISPR nucleases to engineer defined haplotypes in order to understand the functional role of these variants. Our approach overcomes the historic barrier of trying to study the affects of specific human mutations in a background of millions of other genetic differences between two individuals. This work is generously supported by the W.M. Keck Foundation.
- Designing permanent inactivators of HIV
We are designing zinc finger, TALE, and CRISPR nucleases to chop up the integrated DNAform of the HIV provirus without affecting any human sequences. Unlike most other anti-HIV therapies, this approach would permanently inactivate the virus. It should also be useful in patients with viruses that use CXCR4, for whom CCR5 entry inhibitors would be ineffective (ie: most infected patients). This work is partly supported by the National Institutes of Health.
- A bad day for Malaria
We are designing TALE and CRISPR artificial transcription factors to manipulate genes in the malaria-causing pathogen Plasmodium falciparum. These tools will allow us to learn a lot more about the function of the 5,000 genes, and hopefully lead directly or indirectly to new targeted therapies. This work is supported by the Bill and Melinda Gates Foundation.
- Targeting the tumor microenvironment of Neurofibromatosis
We are designing TALE transcription factors that will be able to home in on plexiform neurofibromas in mice and disrupt the tumor microenvironment. Existing data suggests this approach should halt or regress these often untreatable tumors. This work is supported by the Department of Defense.
- High-throughput investigations of zinc finger-DNA interactions
We have developed a high-throughput assay called Bind-n-Seq, and are using it to study the binding affinity and specificity of engineered and natural zinc finger proteins. We are using bioinformatics, protein structure analysis, and biochemistry to understand the zinc finger-DNA recognition code, so that we can predict the binding sites and functions of uncharacterized zinc finger proteins.