CRISPR gene editing is widely recognized as the most significant and groundbreaking breakthrough in life science since the 21st century. It was officially born in 2012 and was recognized by the Nobel Prize in just 8 years. At the end of last year, the first CRISPR based gene editing therapy was approved by the FDA for use in the treatment of sickle cell disease β- Mediterranean anemia has opened a new chapter in the treatment of genetic diseases.
In recent years, the rapid development in the field of artificial intelligence is expected to lift the constraints of natural evolution on gene editors, thereby helping to design more adaptable and powerful gene editors.
On April 22, 2024, AI protein design company Prolunt announced the launch of the OpenCRISPRTM program, releasing the world’s first open-source artificial intelligence generated gene editor – OpenCRISPR-1.
Just like ChatGPT based on the big language model can generate a new article, the big language model can also generate brand new proteins. Now, Prolunt has demonstrated a gene editor designed entirely from scratch by artificial intelligence and has successfully edited the human genome for the first time.
It is worth mentioning that OpenCRISPR-1 is open source and can be used not only for scientific research but also for commercial purposes for free. This paves the way for improving the accessibility of gene editing therapy and reducing the cost of gene editing therapy, helping to accelerate the development of treatment methods for thousands of genetic diseases that are currently incurable. It should be pointed out that Prolunt has opened up gene editing tools generated by artificial intelligence, but has not yet opened up this artificial intelligence technology.
Prolunt is an AI protein design company founded in 2022, dedicated to designing new proteins from scratch through artificial intelligence, in order to develop breakthrough drugs and therapies. Its AI tools based on the big language model can read and write any type of protein, including enzymes, gene editors, antibodies, and the entire protein universe. At present, the company has completed a total financing of 44 million US dollars.
This startup used a Large Language Model (LLM) trained in large-scale sequences and biological backgrounds to generate millions of different non natural CRISPR like proteins, exponentially expanding almost all known CRISPR families. The company’s achievements are an important milestone in the field of gene editing, with the potential to accelerate the development of precision treatments for various genetic diseases.
The specific situation of OpenCRISPR-1 has been published on the preprint platform bioRxiv, and the paper title is: Design of highly functional gene editors by modeling the universe of CRISPR Cas sequences.
Generate multiple CRISPR related protein families
SpCas9 is a CRISPR nuclease from Streptococcus pyogenes and is currently the most widely used gene editor. It targets and cleaves the double stranded DNA of the target site under the guidance of guide RNA (gRNA), thereby achieving efficient gene editing. OpenCRISPR-1, generated from scratch by artificial intelligence, is composed of Cas9 like protein and gRNA. The amino acid sequence of this Cas9 like protein has 400 mutations compared to SpCas9 and nearly 200 mutations compared to any other known natural CRISPR related protein, but it exhibits gene editing activity and specificity comparable to or better than SpCas9.
The research team provided a detailed description of the generation and characterization of OpenCRISPR-1. In the human HEK293T cell line, OpenCRISPR-1 delivered through plasmids exhibits gene editing efficiency and higher specificity comparable to SpCas9 in editing and off target detection of various genomic targets (significantly reducing off target rates in some editing sites).
In addition, when combined with deaminases generated by AI, OpenCRISPR-1 can also perform base editing, displaying robust A-to-G editing at a set of target sites.
Gene editing generated in human cells
Currently, Prolunt is studying the specificity and behavior of OpenCRISPR-1 in the form of purified ribonucleoprotein (RNP) complexes at the genome-wide level. OpenCRISPR-1 is the first version, and Prolunt encourages people to use and test OpenCRISPR-1 and provides feedback to help iterate and advance the OpenCRISPRTM program.
Ali Madani
Dr. Ali Madani, co-founder and CEO of Prolunt, stated that attempting to edit human DNA using artificial intelligence designed biological systems is a scientific lunar landing project, and our success points to a future where artificial intelligence can precisely design what is needed to create a series of customized treatment methods for diseases.
The structure of the OpenCRISPR-1 complex, the world’s first open-source gene editor designed by artificial intelligence
It should be pointed out that although gene editors generated by artificial intelligence have great potential, they are unlikely to affect the pharmaceutical industry in the short term, as they still require further safety and effectiveness proof in preclinical and clinical studies.
However, the rapid development of generative artificial intelligence technology based on big language models has shown us a future where drugs and treatment methods can be quickly tailored to individuals. The breakthrough achieved by Prolunt marks the beginning of a new era of gene editing, in which artificial intelligence plays a core role in designing tools that could revolutionize medicine. With the continuous development of this technology, it is expected to bring us closer to a world where precise treatments for genetic diseases are easier to obtain and more effective than ever before.
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