CRISPR-Cas9: The Gene
Editing Technology Striving for Perfection
Recently, a research
titled “Correction of a pathogenic gene mutation in human embryos” was
published on Nature. This groundbreaking, phenomenal research discovery captures
CRISPR-Cas9 as the most promising genome editing technology.
CRISPR (Clustered
Regularly Interspaced Short Palindromic Repeats)-Cas9 (CRISPR-associated genes)
is a stable form of ribonucleoprotein complex which is composed of the Cas
nuclease Cas9 and the specific guide RNA (gRNA).
MECHANISM OF
CRISPR-CAS9
Primarily, the enzyme
Cas9 acts as a pair of ‘molecular scissors’ that can cut the two strands of DNA
at a specific location in the genome so that bits of DNA can then be added or
removed. The gRNA, which consists of a small piece of pre-designed RNA sequence
located within a longer RNA scaffold. The scaffold part binds to DNA and the
pre-designed sequence ‘guides’ Cas9 to the right part of the genome, making
sure that the Cas9 enzyme cuts at the right point in the genome. The gRNA finds
and binds to a specific sequence in the DNA with the complementary bases. Then,
as the Cas9 follows the guide RNA to the same location in the DNA sequence and
makes a cut across both strands of the DNA. The cell during the checkpoint recognizes
that the DNA is damaged and attempts to repair it.
UNINTENDED MUTATIONS
According to the
Columbia University Medical Centre, CRISPR-Cas9 gene-editing technology may
cause hundreds of unanticipated mutations into the genome. Although CRISPR is
renowned for its preciseness, it could alter other parts of the genome. When
CRISPR is performed in cells or tissues in a dish and under predictive
algorithms, it demonstrates perfection; however, when it is deployed in living
animals, the incomplete genome sequencing can cause off-target effects. In
fact, the researchers identified that CRISPR had successfully corrected a gene
that causes blindness, but it also caused more than 1,500 single nucleotide
mutations and more than 100 larger deletions and insertions which were not
predicted by computer algorithms. These striking side-effects may cause
potentially crucial mutations.
ERASING HEART DISEASE
DEFECT IN HUMAN EMBRYOS
The new results
demonstrated a major advance compared with earlier researches. In the new
researches, scientists succeeded in eliminating the off-target effects of
CRISPR-Cas9. To eliminate the mosaic phenomenon, the CRISPR-Cas9 gene editing
materials were inserted before the fertilization process. In other words, the
sperm with the mutated MYBPC3 gene was inserted along with the CRISPR-Cas9 in
the oocyte during the M-phase, realizing the germ-line editing. Consequently,
this gene editing technology successfully and completely cancelled out the heart
disease defect in the embryo, avoiding the formation of a mosaic embryo.
KSJ
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