CRISPR can generate unexpected, heritable mutations

The conspiracy theorists' warnings came true again. CRISPR-Cas9,
the "genetic scissors," creates new potential for curing diseases,
but treatments must be reliable. In a new study, researchers have
discovered that the method can give rise to unforeseen changes
in DNA that can be inherited by the next generation. These scientists
therefore urge caution and meticulous validation before using
CRISPR-Cas9 for medical purposes (https://bit.ly/3sakFoc).
CRISPR-Cas9 is an effective tool for genome modification in
microorganisms, as well as animals and plants. In health care, the
method creates scope for curing numerous genetic diseases, provided
the DNA is modified correctly and undergoes no unexpected changes.
To date, such unwanted mutations have been studied in cells, but
knowledge of the consequences in living organisms remains limited.
"In this project, we studied the effects of CRISPR-Cas9 in zebrafish,
a small aquarium fish. Since DNA molecules and their mechanisms
are similar in all animals, we think the results should be similar in
humans, for example," says Adam Ameur, associate professor at
Uppsala University and the Science for Life Laboratory (SciLifeLab).
When they studied the genome of more than 1,000 zebrafish from two
generations, the researchers found unexpected mutations of various
types. In some cases, DNA fragments that were larger than anticipated
underwent changes, while in other cases mutations occurred in the
wrong location in the genome. Unforeseen mutations were found in
first-generation zebrafish, but also in their offspring.
"Knowing these unexpected mutations are heritable is important, since
they can have long-term consequences for future generations. But that
can happen only if you change the genome of embryos or germ cells,"
says Ida Hoijer, Ph.D. of Uppsala University and SciLifeLab.
In healthcare, methods tailored to correct genes in a particular tissue
or cell type are now being developed. Although such treatments pose
no risk to future generations, caution is advisable.
"CRISPR-Cas9 can be an amazingly valuable tool in health care. But
we need to minimize the risk of unwanted effects, and we can do this
by carefully validating the modified cells with the latest DNA
sequencing technologies," Ameur says.