Discovery of the CRISPR Gene
Editing System |
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1987 - Yoshizuma Ishiro observes repetitive DNA
sequences in E. coli & later in Archaean species. |
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1992 - Franciso Mojica
analyzes these repeats & coins term CRISPR 'clustered regularly interspaced palindromic
repeats' |
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2002 - the DNA repeats are
shown to occur near CAS nuclease genes that can unwind
& cut dsDNA |
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next - DNA
sequencing showed that the repeats came from bacteriophage
DNA, likley by infection & integration |
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2007 - P. Hovrath & R.
Barrangou of yogurt producer Danisco studying
bacteriophage infections of yogurt bacteria showed infections added new viral spacer DNA & their removal affected ability of yogurt bacteria to resist infections. The viral DNA made RNA pieces that guided CAS nucleases to attack the invading DNA and cut it up... 'a kind of bacterial immune system providing resistance to viral infections'. CRISPR sequenes have subsequently been found throughout microbial life systems. |
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2008 - 1st CRISPR
conference @ Berkeley and speculation grows that the
bacterial CRISPR system might be used to not only target viral DNA for cutting, but any DNA with a "guide sequence". |
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next
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2011 - a. the essentials of how CRISPR works in bacteria are known and Emmanuelle Charpentier identifies an essential RNA component 'tracrRNA of unknown function. b. Eva Nogales, Doudna's colleague describes crystalline structure of the molecules c. V. Siksnys (Vilnius U.) identifies a CAS-9 nuclease as the enzyme that cuts DNA d. Jennifer Diudna & Emmanuelle Charpentier meet at conference in Puerto Rico and begin a collaboration |
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2012 - Dounda &
Charpentier publish in Science that the system requires 2 RNA structures to
have Cas9 make double strand cuts, a guide crRNA and a tracrRNA, which can be combined in a single transcript to cleave any DNA target binding sequence with complementarity to a gene, offering a methodology based on RNA-programmed Cas9 (that has considerable potential for gene-targeted editing applications). |
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2013 - Feng Zeng of Broad
Institute showed that the Doudna methodology worked in
mouse and human cells in culture. By end of 2013 Zeng's group had 64,571 unique CRISPR sequences for some 18,080 Human genes (80% of the Human genome) with a 50% to 80% effectiveness. |
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2020 - Jennifer Doudna and
Emmanuelle are awarded the Nobel Prize in Chemistry
for the development of a method for genome editing. |
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current - The CRISPR
system is easy to use and editing can today be done in
almost any lab. Even CRISPR Kits are available to edit genes. Addgene ("the Amazon for Plasmids") is a non-profit that distributes some 60,000 plasmids of various constructs (CRISPRs) to 20,000+ labs in 85 different countries for researchers to use. But, to date no CRISPR 'health' products to cure any illness are on the market. The US Patent Office has 6,000+ CRISPR patent applications pending. |
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