Therapeutic strategies for autism: targeting three levels of the central dogma of molecular biology

The past decade has yielded much success in the identification of risk genes for Autism Spectrum Disorder (ASD), with many studies implicating loss-of-function (LoF) mutations within these genes. Despite this, no significant clinical advances have been made so far in the development of therapeutics for ASD. Given the role of LoF mutations in ASD etiology, many of the therapeutics in development are designed to rescue the haploinsufficient effect of genes at the transcriptional, translational, and protein levels. This review will discuss the various therapeutic techniques being developed from each level of the central dogma with examples including: CRISPR activation (CRISPRa) and gene replacement at the DNA level, antisense oligonucleotides (ASOs) at the mRNA level, and small-molecule drugs at the protein level, followed by a review of current delivery methods for these therapeutics. Since central nervous system (CNS) penetrance is of utmost importance for ASD therapeutics, it is especially necessary to evaluate delivery methods that have higher efficiency in crossing the blood-brain barrier (BBB).

Automated summary

Significant progress has been made in identifying risk genes for Autism Spectrum Disorder (ASD) in the past decade, specifically loss-of-function (LoF) mutations. However, there has been a lack of clinical advancements in ASD therapeutics. To address this, various therapeutic techniques are being developed to rescue the effects of these mutations at the DNA, mRNA, and protein levels, including CRISPR activation (CRISPRa), gene replacement, antisense oligonucleotides (ASOs), and small-molecule drugs. Delivery methods that effectively cross the blood-brain barrier (BBB) are crucial for successful ASD therapeutics.