Will gene editing be restricted and gene therapy will be affected?
Recently, an international committee issued a report emphasizing that gene editing technology cannot be used to edit human embryos because the safety and effectiveness have not yet reached the standard, at least the edited embryos cannot be implanted into the uterus for reproductive purposes——
"Gene editing is a revolutionary technology for humans. In the future, humans can overcome many diseases that are incurable now through this technology, and even this gene editing technology will change our planet." Nankai University Pharmaceutical Chemistry Biology Shuai Ling, a distinguished researcher and doctoral supervisor of the State Key Laboratory, said with emotion.
However, recently, an international committee issued a report stating that heritable human genome editing (HHGE) currently does not meet the relevant standards for safe and effective application in humans. Countries should expand extensively before deciding whether to approve such technologies for clinical application. Discussion and strict supervision.
According to the "Science" magazine, the report emphasizes that gene editing cannot be used to edit human embryos, at least not for reproductive purposes.
After the release of this report, it has attracted widespread attention. At present, many biotech companies around the world are conducting research and development of gene therapy, and some have even entered the clinic. Will this report affect the development of gene therapy?
Gene editing is a key part of gene therapy
"Gene editing technology has a history of more than half a century, but its real development is accompanied by the emergence of the CRISPR gene editing technology called'gene magic shear'." Shuai Ling said, the previous gene editing required DNA double The homologous recombination of strands requires physical and chemical methods to break DNA double-strands. The probability of such breaks is very low, and the probability of homologous recombination is also very low.
CRISPR is a repetitive sequence in the genome of prokaryotes. It is an immune weapon produced by the struggle between bacteria and viruses in the history of life evolution.
Shuai Ling explained that viruses can integrate their genes into bacteria, and use bacterial cell tools to serve their own gene replication.
However, in order to prevent the invasion of viruses and eliminate foreign genes from invading viruses, bacteria themselves will evolve the DNA cutting mechanism, which is the CRISPR-Cas9 system. Using this system, bacteria can quietly remove foreign virus genes from their genomes. Upper excision.
"Using the Cas9 protein, humans have improved gene editing technology, which can cut a small RNA as a guide tool into DNA, so that the gene can be cut or changed at a specific point. This greatly improves the accuracy and efficiency of gene editing." Shuiling It is said that the previous gene editing was done through genetic mutagenesis, and the final product was unsure, and the application of CRISPR could make precise genetic modification.
"Gene editing may sound'high cold', but in fact, the gene therapy we usually hear from doctors is the application of gene editing technology." Shuai Ling said that at present, gene editing technology is widely used in the medical field. The first application area is the treatment of blood diseases.
"However, gene editing is not equal to gene therapy. Gene therapy is a technology that modifies human genes to treat or cure diseases. It requires a lot of biotechnology to complete, such as cell culture, immunotherapy, gene vectors, etc., but gene editing is gene An indispensable key part of therapy." Shuai Ling explained.
Editing somatic cells does not involve ethical disputes
The report repeatedly emphasized that “Once the genome of a human embryo is edited, unless there is definite evidence that precise changes to the genome can bring reliable results and will not lead to unexpected changes, it should not be used for reproduction.” “This'design' Infants' involve ethical and various technical issues-the main danger of editing human embryos is that there will be unexpected'off-target effects', and these DNA changes cannot be detected before the embryo is implanted into the mother."
"The reason why the genome of human embryos cannot be edited at present is mainly due to ethical issues." Shuiling said that after a human embryo is fertilized, nerve cells will develop within 14 days. In theory, it is a human being. In principle, it cannot be modified. .
In the clinic, there have been experimental studies on gene editing of abnormal embryos, and strictly speaking, it was a marginal shot.
"There is also an off-target effect. For example, we want to delete the A gene, but the B gene is ultimately deleted. This problem cannot be solved well at present." Shuiling introduced.
"In addition, all life phenomena are complex regulatory processes of multiple genes and multiple networks. With the current human research on genes, it is not possible to fully understand the purpose of each gene." At present, gene editing of human embryos is mainly used for research. Purpose, for example, in 2017, researchers at Oregon Health and Science University (OHSU) used CRISPR technology to genetically edit the DNA of a large number of single-cell embryos. The edited embryos did not implant in the uterus, but it was proved through experiments that the correction caused In the defective gene process of genetic diseases, CRISPR technology is both safe and efficient.
"Any technology used in clinical practice should first conduct a good safety assessment." Shuiling said, the current gene therapy for human somatic cell gene editing, such as human tissues, organs, etc., is not used to produce a person , There will be no ethical issues involved.
"In fact, gene editing is not terrible, the terrible thing is to use human embryos for gene editing." Shuai Ling thinks.
Gene carriers and immune rejection are still unsolved problems
In the past half century, gene therapy has absorbed almost all the results of biotechnology, and it has brought new options for the clinical treatment of tumors and genetic diseases.
"Off-target effects are only a problem that gene editing cannot solve at present. Gene therapy involves more technologies, and there are some difficulties in each link that need to be resolved." Shuiling introduced.
For example, gene therapy often requires the help of vectors to deliver therapeutic genes to specific tissues and organs, so an ideal vector is also the key to gene therapy.
"Commonly used gene therapy vectors are divided into two categories: viral vectors and non-viral vectors." Shuiling introduced that viral vectors are widely used, including retrovirus (RV), lentivirus (LV), and adenovirus ( ADV) and adeno-associated virus (AAV), etc.
According to statistics, 13 of the gene therapy products already on the market are based on viral vectors and only 3 are based on non-viral vectors.
Viral vectors also have risks such as insertional mutagenesis, carcinogenesis, increased immune response and inflammation.
In addition, there are high technical barriers to the large-scale production of viral vectors.
Although non-viral vectors have the advantages of low immune prototypes, low cost, and easy scale, they have better clinical application prospects, but there are still many unresolved problems, such as low transfection efficiency, high cytotoxicity, and targeting. Not superior.
"Before the gene editing clinical treatment is fully realized, it is necessary to solve a series of problems including how to achieve high delivery efficiency, how to achieve high-capacity vectors and achieve efficient delivery, and how to provide transiently high expression vectors," said Shuiling.
In addition, the immune response is also a major problem in gene therapy.
Any foreign body that enters the human body will be attacked by the immune system. Cells modified by gene therapy are no exception, which reduces the efficacy.
Finding an appropriate amount of virus injection, which can not only avoid the attack of the immune system, but also produce a therapeutic effect, has also become the direction of scientists' efforts.
Although the current difficulty is still great, gene therapy has a bright future.
For example, Shuai Ling said, for example, some congenital deafness is caused by genes, and gene modification can be used to treat this disease. At present, it has been successful in mice.
In addition, due to the specificity of tumors, it is difficult to treat them with certain drugs.
At present, it is mainly surgical operation, but it is difficult to remove cleanly and easy to relapse.
If gene therapy is used to fundamentally eliminate the genes that cause cancer, the goal of cure can be achieved.
"If the 20th century is the era of drug therapy, then the 21st century is the era of cell and gene therapy coexistence." Shuai Ling said that although there are various limitations in editing human embryos, we should be full of confidence in the development of gene therapy.