Site directed RNA editing to correct disease-causing point mutations


Graziano Pesole



Department of Biosciences, Biotechnologies and Environment, University of Bari, Italy



RNA editing is a relevant epitranscriptome mechanism by which cellular RNAs are modified in specific localizations in a not-transient fashion. In humans, RNA editing involves the deamination of cytosine in uridine by APOBEC enzymes and, most frequently, the conversion of adenosine in inosine by the ADAR family of enzymes (PMID: 29692414). A-to-I editing in non-coding regions is important in modulating the innate immune response, while modifications in protein coding genes has several functional and physiological implications (PMID: 29692414). Indeed, the deregulation of RNA editing in specific genes has been linked to cancer and a variety of neurodegenerative disorders such as Alzheimer and amyotrophic lateral sclerosis (ALS) (PMID: 21682836).

Recently, RNA editing enzymes have been deeply investigated because deaminases domains can be engineered for site-directed RNA editing (PMID: 29967493) and harnessed to correct pathological point mutations as a novel and promising therapeutic approach.

Site-directed RNA editing approach comes with several benefits: i) can correct a mutation in a target gene by guide RNAs; ii) is useful in all human disorders in which the correction has to be modulated in the intensity and during the time; iii) can be used in post-mitotic cells, like neurons, in which the CRISP-Cas technology cannot be applied (brain, heart, skeletal muscle) (PMID: 29967493); iv) lowers the risk for permanent genomic changes because it does not modify the DNA of the target cells and avoids CRISP-Cas side-effects.

Our project aim is to develop RNA editing deaminase-based constructs to correct pathological mutations at RNA level in human cells in which the CRISPR-Cas technology cannot be applied.

Relevant Publications 

  1. Fonzino A, Pesole G, Picardi E. Profiling RNA Editing in Single Cells. Methods Mol Biol. 2023;2584:347-370. doi: 10.1007/978-1-0716-2756-3_18. PMID: 36495460

  2. Picardi E, Mansi L, Pesole G. Detection of A-to-I RNA Editing in SARS-COV-2. Genes (Basel). 2021 Dec 23;13(1):41. doi: 10.3390/genes13010041. PMID: 35052382; PMCID: PMC8774467


Related Projects

PI: Barbara Storti