Scientists from China, South Korea and the U.S. succeeded in safe correction of the gene mutation in early human embryos that results in hypertrophic cardiomyopathy by using CRISPR/Cas9 genome editing technique for the first time on August 3. Such technique has now been popular in the world and named "magic scissors"; it was listed as one of Science’s Top 10 Breakthroughs of 2013; it was re-selected as topping Science’s Top 10 Breakthroughs of 2015. CRISPR/Cas9 technique, compared to the traditional genome editing techniques, integrates the simplicity and precision of genome editing, and has advantages like high efficiency, low cost and ease of operation which lay its current leading position in genome editing field.

CRISPR/Cas9 technique integrates the simplicity and precision of genome editing.

This most potential and revolutionary invention in modern medical field has distinguished itself in the worldwide biomedical research field and gene therapy field, and this technique is widely applied to realize DNA knockout, activation, modification, and mutation, etc. inside cells, tissues or individuals.

Free imagination and attempt of "magic scissors" technique in gene therapy field

The gene therapy field is one of the important application fields of the genome editing technique. According to statistics, there are about 6,000 diseases caused by gene mutation, wherein, only less than 5% have the corresponding therapeutic regimens. According to research, most genes lose the corresponding gene function after the mutation, however, it is quite difficult for traditional medicines to solve the function loss caused by gene mutation, in theory or in reality. Fortunately, new techniques including the genome editing provide brand new solutions for the treatment of such diseases. Theoretically, the genome editing technique can be used to correct mutant genes on DNA molecule level, thereby restoring the functions lost by the organisms: this is a disease treatment regimen with high feasibility and low difficulty, especially, the advantages of the "magic scissors" technique provide natural convenience for the solution of such unmet medical need.

The "magic scissors" technique is much favored by the industry and capital owing to its disruption to the disease treatment modes. Startup gene therapy companies, based on the applications of new techniques in gene therapy field, represent the future market segment with high growth expectations in the pharmaceutical industry. Currently, the three major players in the CRISPR/Cas9 genome editing technique field, i.e., the startup gene therapy companies: Editas Medicine, Intellia Therapeutics and CRISPR Therapeutics, all have completed IPO and entered the capital market. Editas Medicine has the strategic focus of the diseases that have been genetically studied thoroughly but are currently without approved therapeutic regimens, and has invested in dozens of projects, with Bill Gates who has been the world's richest person for many times as one of investors of Editas Medicine; Intellia Therapeutics mainly devotes itself to the development of CRISPR/Cas9 technique in the therapeutic field, like leukemia and cancers; CRISPR Therapeutics focuses on research of breakthrough therapies in disease areas like hemophilia, blindness and congenital heart disease.

Besides capital’s chasing, pharmaceutical industry giants including Novartis, Bayer and Pfizer, etc. have strengthened the research and cooperation in this technical field in succession via many ways.

Half brine, half flame

The thriving is only a side of the present "magic scissors" technique, while the infinite controversies are the other side of this technique.

One of the major issues of the "magic scissors" technique is how to avoid or reduce the gene mutations brought by this technique in non-targeted areas, which is much controversial. A paper titled Unexpected mutations after CRISPR-Cas9 editing in vivo published on Nature Methods this May has thrown cold water on the unbridled enthusiasm in the "magic scissors" technique field. Although 7 famous scientists from global top institutions like Harvard University and MIT co-authored a paper to disprove the serious misleading of the above paper on July 5, regardless of the rights and wrongs of the above event, the off-target effect of the "magic scissors" technique is indeed one of biggest hidden perils of the technique—Cas9 enzyme sometimes cuts in the non-targeted areas, resulting in serious consequences.

A harder truth is that the present scientific evidence shows that the detrimental variations triggered by CRISPR on living animals may be more extensive than we image, and furthermore, humans are still not clear about what the negative impacts of genome editing technique will mean.

However, there is certainly good news. According to report, the research team joined by Jennifer Doudna, one of the inventors of CRISPR/Cas9 technique, proved that an anti-CRISPER protein named AcrIIA4 could reduce the incidence of off-target effect by 4 times, with the genome editing of the target site not affected at all during the entire process. The research paper titled Structural basis of CRISPR–SpyCas9 inhibition by an Anti-CRISPR protein published by the research group from Harbin Institute of Technology led by the scientist Professor Huang Zhiwei has explained on the structural basis of SpyCas9 inhibition by Anti-CRISPR protein including AcrIIA4.

Half brine, half flame may describe the current real situation of the "magic scissors" technique. The application of the new techniques that explore the fields unknown to humans is never going to be easy.

By Xiaoyaowan