A5054146264- CRISPR and Genetic Engineering
- Advanced biosensing and bioanalysis techniques
- DNA Repair Mechanisms
- RNA Interference and Gene Delivery
- Genetics, Aging, and Longevity in Model Organisms
- Epigenetics and DNA Methylation
- Cytomegalovirus and herpesvirus research
- DNA and Nucleic Acid Chemistry
- PARP inhibition in cancer therapy
- Pluripotent Stem Cells Research
- T-cell and B-cell Immunology
Yale University
2020-2024
Brigham and Women's Hospital
2024
Rockefeller University
2018
Despite the rapid and broad implementation of CRISPR-Cas9-based technologies, convenient tools to modulate dose, timing, precision remain limited. Building on methods using synthetic peptide nucleic acids (PNAs) bind RNA with unusually high affinity, we describe guide (gRNA) spacer-targeted, or 'antispacer', PNAs as a tool Cas9 binding activity in cells sequence-specific manner. We demonstrate that rapidly efficiently target complexed gRNA spacer sequences at low doses without design...
Although CRISPR-Cas9 gene therapies have proven to be a powerful tool across many applications, improvements are necessary increase the specificity of this technology. Cas9 cutting in off-target sites remains an issue that limits CRISPR's application human-based therapies. Treatment autosomal dominant diseases also challenge when mutant alleles differ from wild-type sequence by only one base pair. Here, we utilize synthetic peptide nucleic acids (PNAs) bind selected spacer sequences guide...
Unusual nucleic acid structures play vital roles as intermediates in many cellular processes and, the case of peptide (PNA)-mediated triplexes, are leveraged tools for therapeutic gene editing. However, due to their transient nature, an understanding factors that interact with and process dynamic remains limited. Here, we developed snapELISA (structure-specific acid-binding protein ELISA), a rapid high-throughput platform interrogate compare up 2688 parallel structure-protein interactions...
Abstract Activation-induced cytidine deaminase (AID) initiates somatic hypermutation (SHM) and class switch recombination (CSR) in B lymphocytes by catalyzing the introduction of deoxyuracil: deoxyguanine mismatches into DNA transcribed Ig locus. Repair pathways then process these to produce point mutations variable region or double-stranded breaks followed deletional recombination. It has been suggested that post-translational modifications on AID mediate a number different decisions,...