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Successful Correction of Genetic Problems In Mice Before Birth Raises Hopes of Similar Treatments For Humans (theguardian.com)
An anonymous reader quotes a report from The Guardian: Gene editing to correct faulty DNA in human embryos has taken a step closer to becoming a reality, with scientists showing it is possible to correct genetic problems in mice before they are born. Researchers used a form of the gene-editing tool Crispr-Cas9 to introduce a mutation into a gene that would otherwise cause lethal liver failure in mice. While the approach has previously been shown to work in mice after birth, the latest study showed it was also possible to make the all-important tweak before they were born. Writing in the journal Nature Medicine, a team of researchers in the US report how they conducted a series of experiments to explore the use of gene editing in mouse fetuses using a modified form of Crispr that can alter single "base pairs" -- the molecules that couple up to form the rungs of the DNA double helix -- but only cuts one strand of DNA when making a change.
After showing it was possible to make a change at a particular spot in the DNA of liver cells in mouse fetuses, the team focused on a condition known as hereditary tyrosinemia type 1. This is a genetic disease that prevents the body from breaking down an amino acid called tyrosine as it should, and can cause death if left untreated. The team took mice with a genetic mutation that produced a similar condition to hereditary tyrosinemia type 1 and bred them, with the mothers kept on a drug called nitisione. The team then injected 26 of the fetuses with a virus carrying the genetic instructions for making the gene-editing tool, and 27 of them with the same virus but without information for the tool. After birth the baby mice no longer received the drug, and the team watched what happened. "In the non-treated mice, they all died by 21 days of life," said Dr William Peranteau, a pediatric and fetal surgeon at the Children's Hospital of Philadelphia who co-led the study. "However, those that had been treated were able to survive until the end of the study at three months, and looked very similar to another group that had not been injected with anything and were kept on the drug. No gene editing was seen in the mothers who had given birth to the mice.
After showing it was possible to make a change at a particular spot in the DNA of liver cells in mouse fetuses, the team focused on a condition known as hereditary tyrosinemia type 1. This is a genetic disease that prevents the body from breaking down an amino acid called tyrosine as it should, and can cause death if left untreated. The team took mice with a genetic mutation that produced a similar condition to hereditary tyrosinemia type 1 and bred them, with the mothers kept on a drug called nitisione. The team then injected 26 of the fetuses with a virus carrying the genetic instructions for making the gene-editing tool, and 27 of them with the same virus but without information for the tool. After birth the baby mice no longer received the drug, and the team watched what happened. "In the non-treated mice, they all died by 21 days of life," said Dr William Peranteau, a pediatric and fetal surgeon at the Children's Hospital of Philadelphia who co-led the study. "However, those that had been treated were able to survive until the end of the study at three months, and looked very similar to another group that had not been injected with anything and were kept on the drug. No gene editing was seen in the mothers who had given birth to the mice.
I can think of many reasons. The article stated that they were interested in diseases that may be fatal before or shortly after birth. So waiting longer would certainly be a bit of a problem.
But many genetic flaws cause the body to grow abnormally. Fixing the genetic flaw won't repair what has already grown incorrectly.
One genetic flaw that I'm familiar with is Myotonic Muscular Dystrophy. It is an interesting one that has a nearly unique cause that should make it a candidate for being among the first to be corrected. It is caused by the presence of a base pair sequence that is sort of against the rules of properly formed DNA, a CTG sequence. During replication, this sequence can get repeated so that CTG becomes CTGCTG, then CTGCTGCTGCTG, etc. Note that since lengthening of the repeated sequence occurs in replication, this is a genetic issue that gets worse over the generations. Lower numbers of repeats aren't a big problem until later life, but in extreme cases the repeats can get into the thousands and cause problems to manifest before birth. In one case I know, the baby was born at 32 weeks due to congenital-onset Myotonic Muscular Dystrophy.
As I understand it, all that would be necessary to fix Myotonic Muscular Dystrophy is to recognize and remove all occurrences of CTGCTG. Nothing has to be inserted in its place. Just chop it out and join the ends of the gap back together.
But, it causes both development issues in many types of body tissues including brain, so you'd want to do it as early in the fetal stages as you can. Otherwise, irreparable harm will be present throughout life despite having fixed the genetic cause.
But wouldn't it be so much easier and safer to *screen* embryos for known genetic defects, rather than patch them with CRISPR?
The real potential for this technique is to introduce new gene alleles that are not present in the parents.
Yes that is terrifying, but with proper regulation, imagine the potential!
If applied broadly, it could raise the socioeconomic status for the children of the most disadvantaged groups, leading to a more equitable society.
Alternatively, given to those who can pay lots of money, it will increase the divide.