News
In silico prediction and in vivo testing of promoters targeting GABAergic inhibitory neurons
Impairment of GABAergic inhibitory neuronal function is linked to epilepsy and other neurological and psychiatric disorders. Recombinant adeno-associated virus (rAAV)-based gene therapy targeting GABAergic neurons is a promising treatment for GABA-associated disorders. However, there is a need to develop rAAV-compatible gene-regulatory elements capable of selectively driving expression in GABAergic neurons throughout the brain. Here, we designed several novel GABAergic gene promoters. In silico analyses, including evolutionarily conserved DNA sequence alignments and transcription factor binding site searches among GABAergic neuronal genes, were carried out to reveal novel sequences for use as rAAV-compatible promoters. rAAVs (serotype 9) were injected into the CSF of neonatal mice and into the brain parenchyma of adult mice to assess promoter specificity. In mice injected neonatally, transgene expression was detected in multiple brain regions with very high neuronal specificity and moderate-to-high GABAergic neuronal selectivity. The GABA promoters differed greatly in their levels of expression and, in some brain regions, showed strikingly different patterns of GABAergic neuron transduction. This study is the first report of rAAV vectors that are functional in multiple brain regions using promoters designed by in silico analyses from multiple GABAergic genes. These novel GABA-targeting vectors may be useful tools to advance gene therapy for GABA-associated disorders.
February 4, 2023
Pitch Perfect 2022 Recap & Winners Announcement
On Wednesday November 9th, 2022, H2i welcomed founders, students, faculty, mentors and more to Pitch Perfect 2022! Marking H2i’s first in-person event since early 2020, just over 50 attendants gathered in-person or tuned in via livestream to watch the finalists pitch for their chance to win. H2i’s Pitch Perfect Competition is an annual Temerty Faculty of Medicine sponsored initiative focused on celebrating and supporting student innovations on health matters. Created to provide pitch competition opportunities specifically for earlier stage startups, it features six early-stage U of T student-led health ventures pitching for a chance to win one of three Student Innovation Fellowships.
November 17, 2022
Hatchery NEST 2022 Demo Day
Over 90% of gene therapy clinical trials fail at the moment. The reasons for failure include adverse effects and low efficacy of the treatment. One of the most significant challenges in gene therapy is the difficulty in targeting transgene expression in specific tissues. One of the factors that control transgene expression is the gene regulatory element. However, optimization of this component is often neglected. This limitation may halt the progression of gene therapy development. The market currently lacks a highly accurate and selective gene therapy products. Our team has developed an algorithm to design cell-type specific gene regulatory elements for gene therapy products in several hours. Currently, biotech and pharmaceutical companies spend lots of time and money on gene therapy development, although there are a lot of risks associated with the field.
September 12, 2022
Re:Pair Therapeutics Finalists
Finalists in Termis Americas Annual Conference and Exhibition
July 13, 2022
