Our core technology is based on pentatricopeptide repeat (PPR) protein engineering. EditForce Inc. provides an alternative option to genome editing and a novel tool for versatile editing of RNA molecules at the genomic scale, called ‘transcriptome editing’ Our mission is to translate our PPR technologies in various biological fields, including basic sciences, therapeutics, agriculture, and bio-production.
Background & Detail
DNA modification and human history
Genome modification techniques have been used by humans for millennia and have been beneficial. A good example is plant breeding in agriculture over the past 6,000 years. Rational DNA manipulation began with the discovery of restriction enzymes in the 1960s. Recently established genome editing technologies using zinc finger, TALE, or CRISPR have enabled rational modification of specific gene(s) in living cells (Box 1).
RNA, an Enigma at Post-genomic era.
The determination of complete genome sequences (DNA) and the transcriptomes (RNA) for a wide variety of organisms have opened a new biological era for understanding of the complex genetic functions that define living entities. Further, recent studies have indicated the importance of RNA for our life. For example, recent analysis of the transcriptome (gene expression studies) revealed that a large part (more than 60%) of the genome is transcribed into RNA, in spite of the proportion of protein coding genes represents only 1.5% of the human genome. One challenge in biology during this century is to understand how DNA/RNA information is utilized by living cells and how we can effectively use this information.
About PPR protein
The PPR protein genes were identified as a gene family prevalent only in land plants. A PPR protein typically consists of a repeating unit of 35 amino acids of PPR arrays. A series of analyses demonstrated that PPR proteins are involved in various gene expression events in a sequence-specific manner. Typically, a single PPR protein targets a single RNA or DNA molecule and is required for RNA stability, RNA splicing, processing, RNA editing, or transcription of chloroplast or mitochondrial genes. Dr. Nakamura at Kyushu University, a founder of EditForce, elucidated the principle of PPR-RNA and PPR-DNA binding mechanisms that one PPR motif corresponds to one nucleotide and the combination of amino acids at three particular positions (residues 1, 4, and ii) defines the nucleotide specificity in a programmable manner. This knowledge provides the rationale for the engineering of custom RNA/DNA binding proteins, which correspond to arbitrary RNA/DNA sequences.
Box1 Genome editing
Genome editing is defined as rational modification of specific gene(s) in living cells. The technology enables fast and effective gene modification, and overcomes many technical bottlenecks of conventional chemical mutagenesis and gene modification techniques. Currently, ZF-, TALE-, CRISPR/Cas-based genome editing tools has been established. The genome editing has already applied the gene modification of various organisms including animals, plants, fishes, and bacteria.