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RNA Editing

RNA Editing

RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...

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Efficient PAM-Less Base Editing for Zebrafish Modeling of Human Genetic Disease with zSpRY-ABE8e

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Multiplex precise base editing in cynomolgus monkeys.

Wenhui Zhang^1,2, Tomomi Aida³, Ricardo C H Del Rosario⁴

¹College of Veterinary Medicine, South China Agricultural University, 510642, Guangzhou, China.

Nature Communications

|May 13, 2020

Summary

This summary is machine-generated.

Researchers precisely edited multiple genes in monkey embryos using CRISPR base editors. This breakthrough enables efficient multiplex base editing for modeling polygenic diseases and advancing gene therapy in primates.

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Area of Science:

Genetics
Molecular Biology
Primate Embryology

Background:

Polygenic diseases arise from numerous genetic variants, necessitating simultaneous modification of multiple single nucleotide variants for accurate modeling and therapeutic strategies.
Current gene editing technologies face challenges in efficiently targeting multiple sites simultaneously, particularly in complex organisms like primates.

Purpose of the Study:

To demonstrate the feasibility of precise, efficient, and simultaneous multiplex base editing in non-human primate embryos.
To establish a method for creating advanced models of polygenic diseases using primate zygotes.
To assess the specificity and efficiency of CRISPR-based base editors in multiplex editing applications.

Main Methods:

Utilized CRISPR-based cytidine and adenine base editors for targeted genetic modifications.
Performed simultaneous multiplex base editing at up to three distinct sites across 11 different genes/loci.
Employed unbiased whole-genome sequencing to evaluate the specificity and off-target effects of the base editing process in cynomolgus monkey embryos.

Main Results:

Achieved precise and efficient simultaneous multiplex base editing of multiple target sites in cynomolgus monkey embryos.
Demonstrated high specificity of the base editing process with no detectable off-target mutations via whole-genome sequencing.
Successfully edited up to three sites across 11 genes in a single experimental approach.

Conclusions:

Multiplex base editing is a feasible and highly specific technology for engineering primate embryos.
This technique provides a powerful new tool for creating advanced in vivo models of complex polygenic diseases.
The findings pave the way for future gene therapy applications and a deeper understanding of genetic diseases in primates.