There is a critical unmet need to define ASD-causing genes and determine how variants in those genes perturb molecular networks leading to disease. This project aims to address these issues using robust functional assays in model organisms designed to uncover disease networks and provide clinical predictive values of large numbers of variants. Christopher Loewen and colleagues expect to provide much needed progress in identifying clinically relevant ASD susceptibility variants to improve our understanding of ASD and potential treatments.

A critical step towards antisense oligonucleotide (ASO) development for haploinsufficiency is the identification of targets that have demonstrable inhibitory effects on the expression of ASD genes. Jonathan Sebat’s team proposes to accelerate ASO development for ASD risk genes using novel high-throughput platforms for target identification, focusing on regulatory RNA targets that can be readily characterized in transcriptome-wide screens.

Even with tremendous advances in understanding of the causes, autism remains mostly without specific treatments. Antisense oligonucleotides (ASOs) are programmable drugs that can target specific mutations. Joseph Gleeson’s lab plans to generate ASOs to target specific ASD-linked mutations and assess these drugs in stem cell models for individualized therapy.