A5004106287- Advanced biosensing and bioanalysis techniques
- Cystic Fibrosis Research Advances
- Neurogenetic and Muscular Disorders Research
- RNA regulation and disease
- RNA Research and Splicing
- Hereditary Neurological Disorders
- Neonatal Respiratory Health Research
- CRISPR and Genetic Engineering
- Energy Harvesting in Wireless Networks
Mount Sinai Hospital
2023
Cold Spring Harbor Laboratory
2021-2022
Stony Brook University
2018-2022
Significance Cystic fibrosis (CF) is caused by mutations in the cystic transmembrane conductance regulator ( CFTR ) gene, which can lead to respiratory failure. To date, there no treatment for CF CFTR- W1282X mutation located on exon 23. Nonsense-mediated messenger RNA (mRNA) decay (NMD) degrades mRNA, leading low levels of functional protein. We developed a cocktail two antisense oligonucleotides (ASOs) that promotes skipping 23 mRNA. The resulting mRNA NMD resistant and preserves reading...
Familial dysautonomia (FD) is a rare inherited neurodegenerative disorder caused by point mutation in the IKBKAP gene that results defective splicing of its pre-mRNA. The weakens 5′ splice site exon 20, causing this to be skipped, thereby introducing premature termination codon. Though detailed FD pathogenesis mechanisms are not yet clear, correcting defect relevant tissue(s), thus restoring normal expression levels full-length IKAP protein, could therapeutic. Splice-switching antisense...
Abstract Low CFTR mRNA expression due to nonsense-mediated decay (NMD) is a major hurdle in developing therapy for cystic fibrosis (CF) caused by the W1282X mutation gene. CFTR-W1282X truncated protein retains partial function, so increasing its levels inhibiting NMD of will likely be beneficial. Because regulates normal many genes, gene-specific stabilization CFTR- more desirable than general inhibition. Synthetic antisense oligonucleotides (ASOs) designed prevent binding exon junction...
Approximately half of genetic disease-associated mutations cause aberrant splicing. However, a widely applicable therapeutic strategy to splicing diseases is yet be developed. Here, we analyze the mechanism whereby IKBKAP-familial dysautonomia (FD) exon 20 inclusion specifically promoted by small molecule splice modulator, RECTAS, even though IKBKAP-FD has suboptimal 5' site due IVS20 + 6 T > C mutation. Knockdown experiments reveal that suppressed in absence serine/arginine-rich factor...
Abstract Mutations in the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene cause (CF), and CFTR-W1282X nonsense mutation causes a severe form of CF. Although Trikafta other CFTR-modulation therapies benefit most CF patients, targeted therapy for patients with W1282X is lacking. The protein has residual activity, but expressed at very low level due to nonsense-mediated mRNA decay (NMD). NMD-suppression read-through are actively being researched mutants. NMD suppression could...
Abstract Low CFTR mRNA expression due to nonsense-mediated decay (NMD) is a major hurdle in developing therapy for cystic fibrosis (CF) caused by the W1282X mutation gene. CFTR-W1282X truncated protein retains partial function, so increasing its levels inhibiting NMD of will likely be beneficial. Because regulates normal many genes, gene-specific stabilization more desirable than general inhibition. Synthetic antisense oligonucleotides (ASOs) designed prevent binding exon junction complexes...