The new Scissors can temporarily edit RNA

Cas13 is at the heart of the RESE system, which uses a special "wizard" to locate RNA in cells.recently, a new system that allows the editing of RNA came into view, expanding the editable range of CRISPR editing tools and greatly improving the ability to target disease-related gene mutations.
The new system, developed by Zhang Feng of the Harvard-MIT Bode Institute and his team, is called RESE(RNA editing system for cytosine-to-urine-specific changes that enables RNA editing from C to U). The results were published recently in Science.
since the advent of CRISPR gene editing technology, people's ability to edit genes has been completely changed. Moreover, these techniques, known as "magic scissors", are seen as a weapon in the treatment of the human terminal illness. Human beings are known to have more than 7,000 rare diseases, hundreds of millions of patients worldwide, about 95% of rare diseases without effective treatment drugs, once the disease is accompanied for life. The scientific community is experimenting with gene editing to solve the problem of rare diseases.
addition, CRISPR technology now covers a growing number of tools that manipulate genes and their expression, including targeting DNA with Cas9 and Cas12 enzymes and targeting RNA with Cas13 enzymes. The CRISPR toolbox also provides a variety of ways to handle mutations.
because RNA has a relatively short survival time, modifying only disease-related genetic mutations in RNA can avoid permanent changes to the genome. In addition, DNA editing mediated by the CRISPR/Cas9 system is still difficult to edit cell types such as neurons, and new methods are urgently needed to treat deadly diseases affecting the brain.Using the inerated Cas13, the
Team directed RECERE to the location of the cytosine base target in RNA transcripts and used new, evolved, editable enzymes to convert unwanted cytosine into urinary glycosides, thereby altering RNA instructions. The team had previously developed REPAIR technology, which converts adenine on RNA into myosine, and on that basis, RESCUE came into being.
, the emergence of RESCUE technology has greatly expanded the target range of crispr tools to cover modifiable site points such as protein phosphorylation site. These modifiable bits are protein-active switches that are found primarily in cellular signaling molecules and cancer-related signaling path paths.
" we need to have a range of precise gene editing techniques for the diversity of disease-caused gene variants. By developing this new enzyme and combining it with CRISPR's programmability and precision, we have successfully filled a gap in the existing CRISPR toolbox. Zhang Feng said.
previously developed RNA editing system, REPAIR, binds CRISPR/Cas13, which targets RNA, to ADAIR2 enzymes and then directs them to specific RNA locations, specifically converting adenine base (A) on RNA into creatine (I). On this basis, Zhang Feng's team improved and upgraded the REPAIR editing system in the lab until it was able to convert cytosine (C) in RNA into urinary glycoside (U).
, the RESCUE system can be directed to any selected RNA and edited from C to U through an optimized ADIR2 component platform. The researchers also applied this new platform to human cells, demonstrating that RESE can target not only 24 clinically relevant gene mutations in synthetic RNA, but also natural RNA in human cells.
, the researchers further optimized RESE to reduce off-target editing while minimizing interference with gene editing within the target.
In addition, the advent of the RESCUE system greatly expands the editable range of CRISPR editing tools, meaning that many modified site points that regulate protein activity and function, such as phosphorylation, glycosylation, and methylation, can be used as editing targets.
Omar Abudayyeh of the McGovern Institute for Brain Sciences, the paper's lead author, points out that unlike the irreversible permanent changes to the genome brought about by editing modifications at the DNA level, one of the great advantages of RNA editing is its reversibleness, because RNA is only an intermediate product of DNA transcription. As a result, RESCUE can take advantage of its unique advantages when temporary, not permanent, changes are needed.
to prove this, the team temporarily activated the β-serial protein and promoted cell growth using RNA-specific bits on RESE-coded β-serial proteins in human cells ,known to be phosphate on protein products. If such changes are permanent, cell growth can spiral out of control and cause cancer. "Now with the RESE system, we can use it for acute injury, temporarily activating cell growth and promoting wound healing." Abudayyeh said.
researchers also looked at the disease-specific variant APOE4.
APOE4 allied gene has been a genetic risk factor for late-haired Alzheimer's disease. APOE2 (both C in APOE4 and U in APOE2) that differ only from APOE4 are completely harmless. As a result, Zhang Feng and his team imported APOE4 RNA into cells and converted both base Cs into U through the RECECE system, thus converting the risk factor APOE4 into harmless APOE2.
In order to further promote the RESE system to clinical applications, and to enable researchers to use RESE for better academic research, Zhang Feng Laboratory plans to share the RESE system with the academic community, and the CRISPR tools previously developed by the laboratory are also shared free of charge with the academic community. Researchers have free access to the technology for academic research through the non-profit granulation library Addgene. (Source: Tang Erdu, China Science Journal)
related paper information: