Transcriptional linkage analysis with in vivo AAV-Perturb-seq

To facilitate high-throughput genotype-phenotype correlations in complex tissues, a team led by Randall Platt PhD, Professor at the Department of Biosystems Science and Engineering at ETH Zurich, developed adeno-associated virus (AAV)-mediated direct in vivo single-cell CRISPR screening or AAV-Perturb-seq.

In an article published in Nature, AAV-Perturb-seq is presented as a tuneable and widely applicable approach to transcriptional linkage analysis as well as high-throughput and high-resolution phenotyping of genetic alterations in vivo.

The team applied the method using CRISPR-Cas9 gene editing and transcriptional inhibition to systematically probe the phenotypic landscape underlying 22q11.2 deletion syndrome in the prefrontal cortex of adult mouse brains. These experiments led to the identification of three 22q11.2-linked genes involved in known as well as previously undescribed pathways regulating neuronal functions in vivo that explain about 40% of the transcriptional changes seen in a 22q11.2-deletion mouse model.

The outcome of this work so far suggests that the 22q11.2-deletion syndrome transcriptional phenotype observed in mature neurons might partially be explained by the broad dysregulation of a class of genes associated with disease susceptibility that are important for dysfunctional RNA processing and synaptic function.

In this webinar, Dr. Antonio Santinha, PhD and first author on the recent Nature article, will present AAV-Perturb-seq, and illustrate how it may be deployed as a flexible and scalable direct in vivo tool to understand genotype-phenotype correlations in the context of disease, with potential applications in identifying novel therapeutic targets.

What you will learn about in this webinar:

• Screening
• scRNA-seq
• Neuroscience

Webinar Programme (CEST time zone):

• 15.00 Welcome and introduction by Karen O'Hanlon Cohrt PhD., Editor-in-chief, CRISPR Medicine News
• 15.05 Dr. Antonio Santinha, Ph.D., / Scientist, ETH Zürich, Switzerland | Transcriptional linkage analysis with in vivo AAV-Perturb-seq
• 15.45 Q & A with Dr. Antonio Santinha
• 16.00 Close by CRISPR Medicine News

Speaker | Title:

Dr. Antonio Santinha, Ph.D., / Scientist, ETH Zürich, Switzerland | Transcriptional linkage analysis with in vivo AAV-Perturb-seq