First-of-its-kind noninvasive CRISPR method knocks out anxiety gene

Good news! When are we able to knock out the sneezing gene or the male facial hair gene?

"... Researchers have developed a novel, noninvasive method of delivering CRISPR/Cas9 gene-editing technology into the brain ... to knock out a gene that causes anxiety. While the technique has so far only been used on mice, the findings open the door to developing new therapeutics, especially for people resistant to medication. ... They say it’s the first successful demonstration of noninvasive CRISPR/Cas9 delivery capable of passing the blood-brain barrier to enable genetic modification. ...
In the current study, the researchers experimented with intranasal delivery of the CRISPR/Cas9 system to ... knock out the serotonin receptor (HTR2A) gene, which modulates the availability of serotonin. ...
The researchers administered a viral vector, an inactivated adeno-associated virus (AAV), into the noses of mice to deliver the gRNA to neurons in the brain so that it could bind to the target HTR2A gene, which Cas9 then cut out. ... The researchers used the AAV9 subtype, a highly efficient vector for delivering cargo to neurons throughout the central nervous system. ..."

From the abstract:

"The expanding field of precision gene editing using CRISPR/Cas9 has demonstrated its potential as a transformative technology in the treatment of various diseases. However, whether this genome-editing tool could be used to modify neural circuits in the central nervous system (CNS), which are implicated in complex behavioral traits, remains uncertain. In this study, we demonstrate the feasibility of noninvasive, intranasal delivery of adeno-associated virus serotype 9 (AAV9) vectors containing CRISPR/Cas9 cargo within the CNS resulting in modification of the HTR2A receptor gene. In vitro, exposure to primary mouse cortical neurons to AAV9 vectors targeting the HT2RA gene led to a concentration-dependent decrease in spontaneous electrical activity following multielectrode array (MEA) analysis. In vivo, at 5 weeks postintranasal delivery in mice, analysis of brain samples revealed single base pair deletions and nonsense mutations, leading to an 8.46-fold reduction in mRNA expression and a corresponding 68% decrease in the 5HT-2A receptor staining. Our findings also demonstrate a significant decrease in anxiety-like behavior in treated mice. This study constitutes the first successful demonstration of a noninvasive CRISPR/Cas9 delivery platform, capable of bypassing the blood–brain barrier and enabling modulation of neuronal 5HT-2A receptor pathways. The results of this study targeting the HTR2A gene provide a foundation for the development of innovative therapeutic strategies for a broad range of neurological disorders, including anxiety, depression, attentional deficits, and cognitive dysfunction."

First-of-its-kind noninvasive CRISPR method knocks out anxiety gene

Genetic modulation of the HTR2A gene reduces anxiety-related behavior in mice (open access)

Fig. 3  Intranasal delivery of AAV9 vectors containing Cas9 and gRNA receptor leads to down-regulation of 5HT-2A receptor mRNA.