03 December 2020
Viral tools for precise neuronal targeting
Published online 19 August 2020
New approach could help DNA-carrying viruses target specific cell populations, treating their dysfunction.
An international team, including researchers at New York University, Abu Dhabi, has developed a simple approach for identifying cell-type-specific enhancers that could hold the key to improved targeting of specific neuronal populations linked to disease.
Enhancers are short DNA sequences that promote gene transcription. The team searched through the genome for enhancer sequences with specific characteristics that were conserved across mammalian species. This led to the identification of three enhancers on the epilepsy-related gene Scn1a that, when attached to virus vectors and injected into mice, were found to be highly expressed three weeks later in three different neuronal cell types in the brain. These cell types also express Scn1a. The findings indicate that enhancers could be used to highlight specific cell populations for further study, and even for treating diseases. Enhancer-carrying viruses targeting Scn1a-expressing cells could eventually play a role in developing therapies for epilepsy, autism, and schizophrenia, for example.
By extending efforts to discover, validate and develop viral tools to target and manipulate additional subtypes of neurons in the brain, Jordane Dimidschstein, of the MIT’s Broad Institute, envisions it will be possible to develop “a toolbox for the neuroscience community to gain access to any subpopulation of neurons, regardless of species, including humans, with unprecedented specificity” and these efforts will help unlock the potential of precision medicine and gene therapy.
Vormstein-Schneider, D. et al. Viral manipulation of functionally distinct interneurons in mice, non-human primates and humans. Nat. Neurosci. https://doi.org/10.1038/s41593-020-0692-9 (2020).