Opinion | Chinese state-of-the-art scientific discovery helps fine-tune gene-editing

By Augustus K. Yeung

Introduction

When it comes to breakthroughs in high-tech research studies, Chinese scientists have often been falsely accused by hostile U.S. government officials of "stealing" or "spying".

In this political context, the present discovery that can significantly improve the efficiency of genome-editing tools is a vindication and a great overjoy for the dedicated Chinese researchers and the nation.

This breakthrough is also a timely encouragement to the current Chinese universities that are responding to President Xi's recent high-profiled call for transformation in China's educational system, making tertiary education more creative, innovative and responsive to the needs of the nation.

Given these broad social and political contexts, the Chinese scientists' discovery in genome-editing is significant that is worthy of attention and admiration.

The following are the details of the discovery, though some of the new terms may sound unfamiliar.

New Discovery Can Improve Efficiency of Genome-editing Tools

Chinese Scientists say they have discovered a new method that can significantly improve the efficiency of genome-editing tools.

The method, called Improving Editing Activity by Synergistic Engineering (or Midas), "robustly and significantly increased" the human gene-editing efficiency of three tools they used, the researchers said.

Moreover, based on Midas, the researchers found new genome editing tools that had higher efficiency and "very low" off-target effects.

The study by researchers from the Chinese Academy of Sciences was published in mainland peer-reviewed journal The Innovation late last month.

The Wide-Ranging Applications of Genome Editing

Genome editing lets scientists change the DNA of many organisms. The technique aims for a wide range of applications, including in the treatment of genetic or acquired diseases, diagnostic testing, and increasing yields of and improving the nutrition of agricultural products.

"Genome editing is one of the most cutting-edge technologies at the present," said Wang Kejian at the China National Rice Research Institute in the Innovation study. "It has a very broad application prospect."

The first genome editing technologies were developed in the late 1900s. Since then, several approaches have been devised, the most recent and well-known one being CRISPR, or "clustered regularly interspaced short palin-dromic repeats" a natural defense mechanism that allows bacterial cells to detect and destroy viruses that attack them.

Different types of CRISPR-associated systems have been discovered, but the most widely used is the CRISPR-Cas9, an enzyme that cuts the DNA in the genome so it can be rewritten.

The CRISPR-Cas9 System is "Faster, Cheaper, More Accurate…"

The US National Institutes of Health described the CRISPR-Cas9 system as "faster, cheaper, more accurate, and more efficient than other existing genome editing methods".

However, most of the newly discovered CRISPR-Cas9 systems showed poor gene editing activity in human cells, which limited widespread use, the study said.

The researchers found Cas12i, a recently discovered CRISPR-Cas system, had good potential for application, because of its smaller size and single RNA structure.

They engineered a Cas12i variant with Midas – the Cas12iMax – which showed robust activity and higher efficiency compared to currently widely used genome editing tools, the researchers said. They then further designed a high-fidelity version of Cas12iMax, or Cas12iHiFi, to minimize off-target effects, which led to changes in the DNA in regions other than the targeted sites.

"Cas12iHiFi exhibited very low off-target effects and maintained nearly 90 percent on-target activity," the researchers said.

The study found that the Midas-engineered variants had a gene-editing efficiency of up to 52 percent, while other variants performed poorly, with an efficiency of less than 15 percent.

The results showed Midas could apply to improve the gene-editing efficiency of Casa nucleases from diverse CRISPR-Cas systems, the study said. ('Midas' touch helps fine-tune gene-editing, scientists say". South China Morning Post. Tuesday, June 7, 2022)

Conclusion

For young readers who are unfamiliar with the inner workings of genetics, the following notes will help to update their basic knowledge of genes.

A gene is a unit of the hereditary material of an organism that provides the genetic information necessary to fulfill a single function. The term was coined by W.L. Johannsen.

Genes were initially conceived as a string of beads comprising the chromosome; they were later defined as lengths of the chromosome that were physically indivisible.

Genetics is the study of heredity and variation in living organisms. The science of genetics is founded on the work of Gregor Mendel, who, in 1865, established the basic laws of inheritance.

In the early 20th century, chromosomes and their genes were established as the carriers of information determining inheritable characteristics, and with the discovery of the structure of DNA in 1953, the molecular basis of genetics was revealed.

Genetics is important in plant and animal breeding and in understanding inherited diseases and abnormalities.

The implications of the Chinese scientists' discovery have far-reaching significance for genetic counseling and genetic engineering: Genetic counseling refers to advice given to those in whose families there is a history of inherited diseases, such as cystic fibrosis and muscular dystrophy. Families at risk are told of their chances of developing the disease, the likelihood of their children being affected, and what means of prevention and treatment of the disease are available.

Genetic engineering refers to alteration of the genetic constitution of organisms, usually bacteria, in order to obtain gene products beneficial to man.

Genetic engineering has also been used to improve crop plants and produce transgenic animals (for example, mice and sheep) containing foreign genes inserted during early embryonic life. Gene replacement therapy, in which genetically engineered genes are inserted into humans to treat cancer and correct inherited diseases, is still at an experimental stage.

For the Chinese researchers, to be able to engage themselves in these century-old studies is a great honor and a huge contribution to mankind.

Thus, in addition to advances in space science, Chinese scientists are now breaking grounds in life sciences.

Hong Kong university students, both undergrads and graduates, shouldn't you be proud of your country, China?

 

The author is a freelance writer; formerly Adjunct Lecturer, taught MBA Philosophy of Management, and International Strategy, and online columnist of 3-D Corner (HKU SPACE), University of Hong Kong.

The views do not necessarily reflect those of DotDotNews.

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