Engineer explains how Nobel Prize-winning CRISPR technique works
CRISPR/Cas systems as gene editors
Many variants of CRISPR/Cas systems have been discovered, engineered and applied to edit genes. There are already over20,000 scientific publicationson the topic.
CRISPR dates back to 1987, when a Japanese molecular biologist, Yoshizumi Ishino, and colleagues discovereda CRISPR DNA sequenceinE. coli. The CRISPR sequence was later characterized by a Spanish scientist, Francisco Mojica, and colleagues, who named it CRISPR, which stands forClustered Regularly Interspaced Short Palindromic Repeats.
While people and animals have evolved complex immune systems to fight viral attacks, single-cell microorganisms rely on CRISPR to find and destroy a virus’s genetic material to stop it from multiplying.
Charpentier and Doudna figured out how to borrow this innate biological capability from microbes and apply it to genetic engineering of bacteria.
In a landmark paper, published online on June 28, 2012, Charpentier and Doudna showed that the CRISPR gene-editing machinery includes two components: a guide molecule that serves as sort of a GPS to find and bind the target gene site on the DNA of an invading virus, which then teams up with a CRISPR-associated protein (Cas) that serves as a molecular scissorthat snips the DNA.
Around the same time,Virginijus Siksnys, a Lithuanian biochemist at the University of Vilnius, made a similar discovery and submitted results for publication that appeared a few months later, inSeptember 2012.Feng Zhang, a biologist at the Broad Institute in Cambridge, Massachusetts, and colleagues showed that CRISPR can be improved and used forediting mammalian cells. He currently owns one of the first patents on using CRISPR for gene editing, which is beingcontestedby Doudna’s institution, UC Berkeley.
Once the DNA has been cut in the right spot, the cell will try to repair the cut. But the repair mechanism is error prone, and oftentimes the cells fail to fix the cuts perfectly, ultimately disabling the gene. Disrupting a gene is particularly useful for studying its function and find out what happens if you stop a gene from working. This technique is also useful for treating cancer and infections, where turning off a gene can potentially stop cancer cells and pathogens from dividing or kill them outright.
During this cutting-repair process, one can fool the cells by providing a new piece of DNA. The cells will then incorporate this piece of DNA with desirable edits into the genetic code. This enables researchers to correct a genetic mutation that causes a genetic disease, or replace a defective gene with a healthy one.
The beauty of CRISPR lies in its simplicity. CRISPR can be easily customized to target any gene of interest, whether it is in plants, animals or people. CRISPR applications range from tools for understanding biology, as diagnostics andas new kinds of therapeuticstoapplications in producing better crops, biofuels and transplantable organs.
Why CRISPR deserved a Nobel Prize
While there is still plenty of room for improvement of these technologies, scientists have already begun testing CRISPR in a number ofclinical trialsfor treating cancer and genetic disorders. CRISPR-based diagnostics have been also been approved by the U.S. Food and Drug Administration under emergency use authorization forCOVID-19 testing.
CRISPR does come with a lot of ethical concerns that warrant caution. For example, in 2018, a Chinese scientist prematurely and unethically used CRISPR for editing human embryos and createdCRISPR-edited babiesthat could pass these genetic alterations to their offspring for generations to come. Some have used the technology forother CRISPR-related DIY biohacksthat raise moreconcerns over regulating the gene-editing technology.
Despite these concerns, CRISPR has huge potential to transform how scientists candetect,treatand eveneradicate diseasesas well as improve agricultural products. Society is already seeing the benefits of this Nobel-winning technology.
This article is republished fromThe ConversationbyPiyush K. Jain, Assistant Professor of Chemical Engineering, Herbert Wertheim College of Engineering, UF Health Cancer Center,University of Floridaunder a Creative Commons license. Read theoriginal article.
Story byThe Conversation
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