Professor Zhang Feng's Nature Sub-published: Editing the Human Genome Needs Caution
Release date: 2017-08-02
In the past few days, the CRISPR field has brought a wave of eye-catching news. Last week, a team from Oregon revised the human embryonic genome in the United States for the first time using CRISPR gene editing technology. Today, a pioneer of the pioneer of CRISPR, in the journal Nature, published in the journal Nature, from the perspective of human genetic diversity, we need to be cautious when applying genome editing techniques to the human body.
Prof. Feng, a pioneer of the CRISPR pioneer, calls for human genome editors to be cautious (Source: Stat)
Briefly introduce the principle of CRISPR gene editing technology. This technology requires two key members, one that is capable of shearing DNA (such as Cas9 and Cpf1) and the other that is responsible for bringing these enzymes to specific regions of the guide RNA (gRNA). Under the influence of these two types of members, the CRISPR system can effectively and efficiently cut the genomic loci selected by the researchers, making large-scale application of genome editing possible. People imagine that with CRISPR gene editing technology, we may soon be able to repair the genes of patients and make them healthy.
But the paper published by Professor Zhang Feng today reminds us that editing human genomes should not be too hasty. He pointed out that human genetic information is diverse. This not only affects the reliability of targeting specific sequences, but also the choice of enzymes. In addition, because of the significant differences in genetic information between people, everyone is also faced with different “off-target risks†(ie, editing in unexpected genomic regions).
Analysis of common pathogenic genes suggests that potential off-target sites are not uncommon (Source: Nature Medicine)
As evidence, Professor Zhang Feng found 12 genes directly related to human diseases and looked for potential off-target sites in these genes. Statistics show that such potential off-target sites are not uncommon.
To this end, Professor Zhang Feng proposed two potential solutions. First, he recommends genome-wide sequencing prior to treatment of patients to understand the safety and effectiveness of CRISPR gene editing techniques for specific patients. Secondly, he also suggested that when choosing the editing site, try to use the sequence with the lowest risk of off-target to ensure safety in the crowd.
Some researchers believe that this paper directly answers the current concerns about the off-target effects of CRISPR gene editing technology. Recently, when an advisory committee of the US FDA evaluated Novartis's heavy CAR-T therapy, it specifically mentioned whether genetic editing would cause additional mutations and induce new cancers. Although this therapy has been unanimously supported by the committee, the human application of gene editing technology is far from being completely relieved.
Dr. Andy May said that this does not mean that we need to sequence all of our genomes in order to develop CRISPR therapy (Source: CrunchBase)
Dr. Andy May is the Senior Director of Genomics Engineering at the Chan Zuckerberg Biocenter (founded by the Zuckerbergs) and he believes that this paper by Professor Zhang Feng is a good discussion. However, he also pointed out that this does not mean that "everyone's genome has been sequenced, we can promote the development of CRISPR therapy." No treatment is zero-risk, the key is whether we can keep the risks firmly in control.
Professor Zhang Feng also holds the same view. In his paper, he proposed that this analysis of human genetic diversity provides a good tool and resource to understand how to improve efficacy and safety. Ultimately, these findings should drive gene therapy into the clinic faster.
Reference material
[1] Implications of human genetic variation in CRISPR-based therapeutic genome editing
[2] CRISPR Pioneer Zhang Preaches Extra Caution In Human Gene Editing
Source: Academic Jingwei
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