A team of researchers from the University of Pennsylvania and Children’s hospital of Philadelphia has seen exciting results in their experiment on mice fetuses with an inherited liver disease. The team removed the amniotic sac containing the fetus from the mother’s uterus, before injecting in a vein of thee fetus near the liver with CRISPR. This was to ensure that the genetic modification would be in the liver cells and would not affect any other vital organs. The fetus was then placed back into the uterus and the mother was thankfully unaffected by the modification, allowing for all the babies to be born without any issues.
The team used a more recently invented form of CRISPR called base editing instead of the well-known CRISPR-CAS9. Rather than cutting and inserting a sequence of DNA, a single nitrogenous base was replaced with another. This newer method showed significantly less “genetic havoc”, unknown consequences for a cell that has been genetically modified with CRISPR.
The disease they targeted was a tyrosinemia type I, a mutation that effects 1 in 100,000 newborns globally, which causes causes the amino acid tyrosine to be metabolized into toxic products, which build up and cause damage to liver, and can eventually destroy it. The scientist sought to disable the HPD gene, which creates enzymes that help to break down tyrosine. By changing a cytosine base to thymine base, the toxic products are never produced.
As the mice grew and developed, the researchers were astounded to find that despite only 15% of their liver cells having been the altered with the base edit, the genetically modified mice were surviving better and gaining more weight compared to those treated with traditional methods of drugs and monitored diet.
This is definitely a step in the right direction to eliminating genetic diseases, but base editing, especially for diseases due to multiple mutations might be more difficult, as many bases would need to be edited. What do you think: more safe, yet possibly difficult base editing method or cut-insert method?