Axonal Regeneration after Silencing a Cytokine Gene

Article: Neurons Regenerated through Suppression of Regeneration-Thwarting Genes
Source: Genetic Engineering & Biotechnology News  and Yale University, via NEI
Published: March 2, 2021

Researchers at Yale University recently identified 40 genes involved in preventing axonal regeneration in the central nervous system in a mouse model. By suppressing those genes, especially the gene for the cytokine interleukin-22 (IL-22), they were able to regenerate retinal ganglion cell axons in a mouse model of glaucoma (by optic nerve crush). The study itself seeks to investigate the larger topic of CNS nerve regeneration, and in this case uses the convenient model of the optic nerve. The authors state, “Reduced IL-22 drives concurrent activation of signal transducer and activator of transcription 3 and dual leucine zipper kinase pathways and upregulation of multiple neuron-intrinsic regeneration-associated genes.” In other words, suppressing this cytokine gene led to favorable expression of regenerative genes. This kind of discovery was facilitated by the advent of DNA cutting technologies, such as the viral-driven short hairpin RNAs used in these experiments; another DNA cutting technology most of us have heard of by now would be CRISPR-Cas9. These gene editing tools allow researchers to observe the function of a gene by silencing it, by rendering the gene nonfunctional through cutting its DNA sequence. The researchers also noted that identifying multiple genes suggests multiple molecular pathways, which could be useful for both multiplexed gene editing (a more efficient method of gene editing) and interventional therapeutics.

My rating of this study: ⭐⭐⭐