Lauren Verhaeghe
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Research Subjects
Lauren Verhaeghe has a total of 12 co-authors. Here are the top co-authors by number of shared publications:
- Ashish R. Deshwar
The Hospital for Sick Children
1 shared publication - Bushra Haque
The Hospital for Sick Children
1 shared publication Chung Ting Tsoi
Program in Genetics and Genome Biology, SickKids Research Institute, Toronto, ON, Canada
1 shared publication- Conor Klamann
Data Sciences Institute, University of Toronto, Toronto, ON, Canada
1 shared publication - David Cheerie
Hospital for Sick Children
1 shared publication - Evgueni A. Ivakine
Genetics and Genome Biology Program, The Hospital For Sick Children, Toronto, Canada
1 shared publication
Latest Publications
- Open Access
A scalable platform for exon-skipping antisense oligonucleotide therapy development for inborn genetic diseases
Antisense oligonucleotides (ASOs) are a versatile therapeutic modality for inborn genetic diseases. ASOs can induce skipping of “dispensable” exons containing disease-causing variants to rescue protein amount and function, but this approach has been studied for only a small number of genes. We developed a high-throughput in silico tool for assessing exon dispensability and designing exon-skipping ASO sequences. Parameters were optimized using known dispensable and in-frame indispensable exons. Across 72,644 exons of 5,057 disease genes, we identified thousands of new targets for exon-skipping ASOs (3.4% of exons with most stringent filters, 24.5% with less stringent filters) that collectively include 0.97%-15.6% of disease-causing variants in large-scale databases. To facilitate recognition of DNA variants potentially amenable to exon skipping as a therapeutic strategy, we established the HAWK-EYE database as a repository of exon dispensability predictions and corresponding in silico -optimized ASO sequences, available as an open-access web application ( https://hawk-eye.research.sickkids.ca/ ). To illustrate translational utility, we experimentally validated a subset of the in silico -optimized ASO sequences that were generated for all Dispensable exons in the HAWK-EYE database, and showed that skipping a Dispensable exon in SOX5 preserves protein function using in vivo and in vitro assays. This scalable platform approach to exon-skipping ASOs will accelerate identification and testing of amenable genetic variants.
Open AccessA scalable platform for exon-skipping antisense oligonucleotide therapy development for inborn genetic diseases
Antisense oligonucleotides (ASOs) are a versatile therapeutic modality for inborn genetic diseases. ASOs can induce skipping of “dispensable” exons containing disease-causing variants to rescue protein amount and function, but this approach has been studied for only a small number of genes. We developed a high-throughput in silico tool for assessing exon dispensability and designing exon-skipping ASO sequences. Parameters were optimized using known dispensable and in-frame indispensable exons. Across 72,644 exons of 5,057 disease genes, we identified thousands of new targets for exon-skipping ASOs (3.4% of exons with most stringent filters, 24.5% with less stringent filters) that collectively include 0.97%-15.6% of disease-causing variants in large-scale databases. To facilitate recognition of DNA variants potentially amenable to exon skipping as a therapeutic strategy, we established the HAWK-EYE database as a repository of exon dispensability predictions and corresponding in silico -optimized ASO sequences, available as an open-access web application ( https://hawk-eye.research.sickkids.ca/ ). To illustrate translational utility, we experimentally validated a subset of the in silico -optimized ASO sequences that were generated for all Dispensable exons in the HAWK-EYE database, and showed that skipping a Dispensable exon in SOX5 preserves protein function using in vivo and in vitro assays. This scalable platform approach to exon-skipping ASOs will accelerate identification and testing of amenable genetic variants.