Genome or gene editing is when targeted changes are made like insertions and deletions, right
in an organism’s genome.
Over the past decade, the CRISPR-Cas9 system has become a very popular method of genome
editing because it’s fast, cheap, precise, and relatively easy to use.
The way it works is that researchers create a piece of RNA with a ‘guide’ sequence
which is complementary to a targeted bit of DNA in the host’s genome.
In other words, if the DNA has a sequence that reads 5′ -GGCTAT- 3′ , then the RNA
guide sequence is exactly the opposite and reads 3′ - CCGAUA -5′ And remember it’s
a U for Uracil instead of a T for Thymidine because the guide sequence is made of RNA
and not DNA.
The Cas9 protein then attaches to the RNA and the whole thing binds to the target DNA
sequence in the host genome.
The Cas9-RNA complex then makes a double-strand cut in the genomic DNA, and an alternative
piece of DNA can be spliced in right at that spot.
CRISPR-Cas9 technology works in a variety of cell types and organisms, and it’s been
used to study diseases, and generate tissues from stem cells, like heart muscle tissue
and neuronal tissue.
Now, it’s also possible to treat a whole, multicellular organism with genome editing.
For example, a mouse with liver disease due to a genetic defect was treated with a CRISPR-Cas9-mediated
genetic change, and it improved the mouse’s symptoms.
One important point to note about this mouse example, however, is that the change was made
to somatic cells, rather than germline cells, meaning these genomic modifications aren’t
passed to the next generation.
That said, CRISPR-Cas9 technology is able to alter the DNA in germline cells, and if
that’s done, then the engineered changes can be transmitted across generations.
And this has been done in several organisms including mice, monkeys, and most recently
in humans.
Last month, Chinese scientist He Jiankui, claimed at a conference that he has edited
the genes of twin girls using CRISPR-Cas9 technology.
He specifically altered the CCR5 gene—making the carrier resistant to some strains of HIV.
He made the change In two embryos which were then implanted in a woman and carried to term.
Reportedly, the unidentified twins were born and are healthy and at home with their parents.
The announcement has lead to an international moral outcry.
First off, Jiankui acted in secrecy and did not even tell his institution about his experiments.
Second, it is not clear if there was proper informed consent from parents before the procedure
was done.
Third the procedure didn’t have a known medical need, since neither of the infants
had an HIV infection, and the procedure inactivated a healthy gene.
Fourth, genome editing technology is still in its infancy, and there’s no global consensus
about using gene-editing technology on human subjects.
In addition, the risks of doing this to human embryos remains difficult to predict.
For example, according to Jiankui’s presentation not every cell in the embryos was edited by
CRISPR-Cas9.
One possible outcome of this is that the twins may be heterozygous for the edited gene, meaning
each cell has a normal and edited copy of the CCR5 genes, in which case they may not
be resistant to HIV.
Another is the twins may be mosaic, meaning that some of their cells have two copies of
the normal gene while other cells have two copies of the edited gene, meaning that they’d
only be resistant to HIV if the immune cells end up having the edited gene.
In addition, the mutation made to the CCR5 gene didn’t exactly match the known variation
of the gene that confers HIV resistance.
This means it’s not clear if these untested changes will provide the same benefits, or
introduce new unintended consequences.
That said, while this research appears to be rushed, and the fallout from it may have
consequences that impact the scientific community for years, there is support for the idea that
germline genome editing of human embryos could someday be used ethically to prevent devastating
genetic diseases like cystic fibrosis or muscular dystrophy.
The general consensus is that we’re not there yet, and that the scientists have moved
quicker than the ethicists.