Edit Force Co., Ltd.
Publication of paper: We have developed an efficient technique for producing genes that express PPR proteins, and realized exon skipping in human cells by PPR proteins.
Editforce Co., Ltd. (Headquarters: Fukuoka City, Fukuoka Prefecture; Representative Director: Takashi Ono; hereinafter referred to as “our company”) has designed a target RNA sequence in collaboration with Professor Takahiro Nakamura, Faculty of Agriculture, Kyushu
University. We have developed a technology to efficiently produce artificial PPR proteins. Furthermore, we demonstrated that exon skipping can be achieved in human cells using the PPR protein produced by this method. A paper on this research was published in the scientific journal Cells on November 8, 2022.
The newly developed PPR production technology has improved the production efficiency of PPR proteins, making it possible to produce and select PPR proteins that are candidates for gene therapy drugs in a short period of time. In addition, exon skipping using PPR proteins opens up the possibility of gene therapy, and is expected to contribute to the development of treatments for various genetic diseases. In the future, we will utilize this technology to expand our drug discovery pipeline and push forward with research and development activities to create new pharmaceuticals.
We have the technology to design PPR proteins that specifically bind to target RNA sequences. Since the PPR protein has a structure in which the PPR motif consisting of 35 amino acids is repeated, it has been difficult to create a gene that encodes the PPR protein, and it has taken a long time to create a large number of high-quality genes. In this research, by optimizing the sequence of the gene encoding the PPR protein, we developed a method that prevents the sequence of the gene encoding each PPR motif from being disturbed during ligation and allows easy ligation. It was also confirmed that the PPR protein obtained has the sequence specificity as designed. Genes designed by this technology can be automated in the production process, and a large-scale PPR protein gene library can be produced in a short period of time. I can do it.
We also demonstrated that exon skipping can be achieved by specifying targets in human cells by taking advantage of the ability of the PPR protein to bind to RNA. Exon skipping is a technology that
artificially removes (skips) part of a group of base sequences (exons) involved in protein synthesis in the process of transcription of messenger RNA from DNA. Proteins are synthesized using messenger RNA as a template, and various proteins are produced in vivo by
intricately changing the combination of exons that make up messenger RNA. Abnormalities such as deletions in exons may prevent normal protein synthesis and cause the development of certain diseases. By applying the results of this study, it may be possible to restore abnormal exon configurations and gene therapy by removing exons with mutations.
◆ Paper information
Yusuke Yagi, Takamasa Teramoto, Shuji Kaieda, Takayoshi Imai, Tadamasa Sasaki, Maiko Yagi, Nana Maekawa and Takahiro Nakamura
Construction of A Versatile, Programmable RNA-binding Protein using Designer PPR Proteins and Its Application for Splicing Control in Mammalian
Cells 2022, 11(22), 3529
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