The development and prospect of "gene magic shear" technology.

Text . . . The star-studded technology that sparked the global storm CRISPR/Cas9 has been in the lith of attention since its inception in 2002.
the technology was named one of Science's Top 10 Scientific Breakthroughs in 2012, 2013 and 2015, and was named one of the top ten most influential technologies of the 21st century by the media, as well as a strong contender for the Nobel Prize.
1 Global publication of CRISPR-themed literature data for 2015-2019 Source: Pubmed CRISPR/Cas9 Development Overview CRISPR Technology Discovery Has been going on for more than 20 years.
First, in 1987, Japanese scholars discovered a series of interval repetition sequences in the alkaline phosphatase gene of E. coli K12;
2002, the technology was officially named CRISPR by Jansen, and the Chinese is "a sequence of short echoes of clustered regular intervals", whereas the nucleic acid intra-cut enzyme commonly used in this system is Cas9.
after six years of research, the link between this repeat sequence and bacterial-obtained immunity was finally demonstrated between 2005 and 2008.
the system, bacteria can silently remove viral genes from their chromosomes, a peculiar immune system.
the end of 2012, Doudna and Chappentier built CRISPR/Cas9, a short RNA-mediated DNA nucleic acid intra-cutting enzyme, for the first time in an in-body system for the study of the authors, marking the advent of CRISPR/Cas9 gene editing technology.
2014, the Broad Institute (Team Zhang Feng) was the first U.S. Patent and Trademark Office to grant the first patent grant for CRISPR/Cas9 technology.
pioneers of CRISPR/Cas9 technology, including Zhang Feng and two female scientists, Jennifer Doudna and Emmanuele Charpentier (pictured below).
Figure 2 Zhang Feng, Doudna, and Charpentier Data Source: Three scientists have received numerous honors and awards, as well as great commercial success: Editas Pharmaceuticals, Intellia Therapeutics and CRISPR Therapeutics", the "Big Three" companies, went public in February, May and October 2016 (a detailed description of the three pioneers and their products will be released to the public next issue).
THE CRISPR/Cas9 patent battle for CRISPR/Cas9 technology patents is more like a legendary story, centered around "the use of CRISPR/Cas9 technology in the ucleocytes."
the war was the first patent grant from the U.S. Patent and Trademark Office on CRISPR/Cas9 technology from the Broad Institute in 2014.
Doudna's patent application for CRISPR/Cas9 technology for editing all types of cells, including bacteria, plants, animals and humans, has been delayed.
Dondna's patent was actually filed about seven months earlier than Zhang Feng's.
because zhang Feng's patent application fast-track, the patent was granted to Zhang Feng's team.
means that Zhang Feng's team has the power to use CRISPR/Cas9 on all creatures except bacteria, including mice, pigs and people.
time forward, as early as 2012, Doudna and Charpentier collaborated to publish crispr/Cas9's article in the journal Science on the precise cutting of bacterial (primary nuclear cell) DNA in test tubes.
only half a year later, Zhang Feng's team published its first crisPR/Cas9 gene editing paper on human cells (etonutional cells) in the journal Science in early 2013.
based on that history, the University of California, Berkeley, filed a lawsuit in 2015 to fight for the right to own the patent.
, the patent dispute officially began.
After more than two years of evidence and debate, in early 2017, the U.S. Patent Office's Review and Appeals Board ruled in a patent dispute over CRISPR/Cas9 technology, ruling that Zhang Feng's Broad Institute retained the CRISPR/Cas9 technology patent it obtained in 2014 without conflict with a patent application from the University of California, Berkeley, which resulted in the loss of the gene editing patents owned by Doudna and Chapinti.
Although the University of California, Berkeley filed an appeal with the U.S. Court of Appeals in July 2018 to challenge the U.S. Patent Trial and Appeals Board's ruling earlier this year, two months later, in September 2018, the U.S. Court of Appeals rejected an appeals court ruling upholding the U.S. Patent Trial and Appeals Board's ruling that the Broad Institute would continue to have intellectual property rights in the use of CRISPR/Cas9 gene editing in true nuclear organisms.
victory in U.S. patent rulings does not mean winning patents elsewhere.
broad institute's fate in Europe is quite different from that of the United States.
January 2018, the European Patent Office revoked the broad institute's underlying patents, meaning that Zhang Feng's team is in danger of losing its dominant position in the intellectual property rights of CRISPR/Cas9 gene editing technology in Europe.
While UC Berkeley's patent victory outside the U.S. is "on the rise," china's State Intellectual Property Office (SIPO) granted the University of California, Berkeley's research team the patent rights to the original nuclear biology and eukaryotes CRISPR/Cas9 gene editing in June 2018, the same patent it filed in Europe and the United States in a legal dispute with the Broad Institute.
The European Patent Office (EPO) also granted the University of California a patent for this broad-based claim.
, of course, the patent dispute is more complicated than people think.
In addition to the University of California, Berkeley and the Broad Institute, Merck Millipore Sigma, Korea's Tool Gen, Lithuania's Vilnius University and Harvard University in the United States are among the six early applicants to the European Patent Office for CRISPR/Cas9 technology patent applications.
the patent battle continues, it will not affect the commercialization of CRISPR/Cas9 technology.
the future of gene editing technology, the development of a drug takes a long time, in addition to proving its clinical effectiveness, but also need to ensure the safety of the drug, a thorough understanding of the adverse reactions of the drug.
, drug development and development processes need to comply with national drug regulatory policies, which also extend the development of drugs to some extent.
drug research and development process for decades.
, however, the use of gene-editing techniques can bring customized therapies to market more quickly and accelerate drug development.
Among other things, CRISPR technology is more convenient and flexible, it can quickly identify potential target genes, by "knocking" or "knocking in" different genes, providing researchers with a faster and more accurate way to study thousands of genes, to determine which genes mutations or expression abnormalities may affect specific diseases, thus making preclinical and clinical trials more efficient.
, single-gene genetic disease is one of the most ideal applications of gene therapy.
for example, single-gene diseases of the blood system, such as beta-thalassemia or sickle cell disease, are ideal targets for gene therapy, which can be treated in-body (also known as introphy).
patients' blood cells can be removed, genetically edited using CRISPR technology, introduced defect-free genes into these cells, and then chemically screened out red blood cells with genetic defects that have been corrected, and transplanted back into the patient for therapeutic purposes.
, gene editing technology has great prospects for application and will occupy a strong market position in the pharmaceutical research and development market in the future.
limitations of gene editing technology is undeniable, any gene editing technology has limitations, whether it is technical risk or ethical risk.
CRISPR technology has the advantages of high efficiency, speed, simplicity, low cost and non-species restriction, it always has unpredictable and uncontrollable off-target risk and is not suitable for complex genetic modification projects.
"gene-edited baby" incident, which has been in full swing for nearly a year, has once again attracted widespread attention from the global genetic community, pushing CRISPR technology to the forefront.
the trial is over, the future impact of the three born gene-edited babies on human society is inestimable.
It is true that the direction of gene technology is to continuously improve accuracy and improve safety, but at present it is still insufficient in accuracy, efficiency and safety, human beings are still a long way from the controlled use of gene editing technology.
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