Activation and Cognition-Enhancing Gene Klotho
Numerous lines of evidence indicate that the antiaging and cognition-enhancing Klotho protein promotes neuronal viability, increases anti-oxidative defense, and encourages remyelination in demyelinated nerves. Upregulation of the Klotho can therefore potentially relieve symptoms or prevent the progression age-associated neurodegenerative disorders such as Alzheimer’s and demyelinating conditions such as Multiple Sclerosis. We used a CRISPR/dCas9 system to test single-guide RNAs (sgRNAs) that target the Klotho promotor region in order to activate the Klotho transcriptionally. We identified two sgRNAs which can enhance Klotho gene expression. Three different systems were used to examine the transcriptional activation. These included a Firefly Luciferase coincidence reporter system and a NanoLuc Luciferase knock-in at the 3′-UTR of Klotho using CRISPR genome editing. We also examined two cell lines that express Klotho in their endogenous form: SY5Y neuronal cells and HK-2 kidney cells. Both sgRNAs increased Klotho protein and gene expression. Our results demonstrate the feasibility of CRISPR-based gene therapy to target Klotho. The therapeutic potential of increasing Klotho levels is to increase cognition, treat age-related neurodegenerative diseases and demyelinating conditions, including chronic kidney disease, and cancer.
Keywords: Alzheimer’s disease, Cancer, Chronic kidney disease, Multiple sclerosis (MS), Myelin and Neuroprotection.
Source:
https://pubmed.ncbi.nlm.nih.gov/29352444/
