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EditForce Realizes RNA-editing Technology of “U-to-C” in Human Cells

publication date: Dec 15, 2022
 | 
author/source: EditForce Inc

editforce-realizes-rnaediting-technology-utoc-human

 

EditForce, Inc. headquartered in Fukuoka, Japan, has realized the world's first RNA-editing technology that enables RNA-editing bases to be changed from "U" to "C," and demonstrated that this technology works even in human cells in a joint study with Professor Takahiro Nakamura, Faculty of Agriculture, Kyushu University.

The study opens up the possibility of editing gene mutations which could not have been the target with the existing technologies, and is expected to contribute to the R&D of therapies for various genetic diseases. EditForce will improve safety and editing efficiency in its development activities to establish innovative gene therapy technologies. The study was published in the scientific journal "Communications Biology" on September 15 (September 16 in JST), 2022.

 

Outline of research

A genome existing in each human cell consists of four nucleotide bases -- A, C, G, and T -- of which the sequence holds the information necessary to make up a human body. Cells generate RNA consisting of four nucleotide bases -- A, C, G, and U -- based on genomic sequences, and then produce protein according to the sequences of RNA. However, changes in a single nucleotide on a genome or RNA sequence cause a variety of diseases. Treatment of these diseases requires single base-editing technology of repairing genomic or RNA mutations to bring the sequences back on the normal track.

Currently, genome-editing technology has been developed rapidly, but the development of editing technology for RNA sequences remains limited. Especially as regards a single base substitution, technologies have been established to substitute "C" with "U" and "A" with "G," but the substitution of other bases is yet to be realized.

The study clarified the mechanism of RNA editing in plants to substitute "U" with "C," based on which EditForce has realized the world's first RNA-editing (base substitution) technology that substitutes "U" with "C," and the company demonstrated that this technology works in human cells.

Base-editing technologies can be applied to the treatment of diseases caused by a single mutation, and "U-to-C" RNA-editing technology of the study opens up the possibility to edit mutations which could not have been the target with the existing technologies. Further, repairing mutations by RNA editing without changes in genome sequence will enable EditForce to provide safer treatments to patients. The company expects that this technology will establish a novel gene therapy by improving safety and editing efficiency in its development activities.

This work was supported by the Research Grant for Young Scholars funded by Yamanashi Prefecture.

 

Article information

Ichinose M., Kawabata M., Akaiwa Y., Shimajiri Y., Nakamura I., Tamai T., Nakamura T., Yagi Y. and Gutmann B. "U-to-C RNA editing by synthetic PPR-DYW proteins in bacteria and human culture cells"

 

About EditForce, Inc.

EditForce, Inc., a Kyushu University-originated venture company developing a unique DNA/RNA-editing technology (PPR platform technology (*)), was established in May 2015 by KISCO Ltd. and Prof. Takahiro Nakamura of Kyushu University (former president of EditForce and currently its scientific advisor) and funded by companies and funds that have track records of investing in life sciences and biotechnology. EditForce aims for drug discovery that applies the PPR technology through joint research with universities and private companies.

 

(*) Pentatricopeptide repeat (PPR) protein platform technology

PPR is a protein discovered in plants that regulates gene expression by binding to DNA and RNA in a sequence-specific manner. The PPR proteins are also found in humans and yeasts, and they have similar functions. Prof. Takahiro Nakamura and Dr. Yusuke Yagi, CTO of EditForce, have focused on the PPR proteins and elucidated the mechanism that determines sequence specificity, and established a technology for creating various PPR proteins, each of which binds to a specific target DNA or RNA sequence. Furthermore, it is possible to manipulate and modify the target genome and RNA both inside and outside the cell by fusion with effector proteins.

 



 

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