Video: Overview of how scientists edit an RNA sequence.
Rett's syndrome is a chronic, neurological disorder that causes repetitive hand movements, and a combination of other complications relating to the respiratory system, loss of speech, and musculoskeletal system. Currently, there is no cure for the disorder, caused by a small error in the DNA code of the MECP2 gene that interferes with the gene producing a functional protein. A new study from the Vollum Institute at the Oregon Health and Science University shows that fixing the RNA code in three different types of neurons restores half the normal amount of the MECP2 protein.
Previous studies from the same researchers show that a synthetic RNA guide can edit mice's genetic code. This study broadens that finding by showing that editing the genetic code is possible in multiple types of neurons and that it achieves the intended downstream effect by restoring MECP2 protein levels.
Most of Rett's syndrome cases are caused by an A replacing a G in the DNA code, but many possible mutations cause MECP2 to lose its function. Researchers design the guide RNA to match each mouse's specific mutation and administer the guide RNA via an enzyme. The RNA approach was successful in three different types of neurons and restored the function of the gene and the presence of the protein.
The next step is to inject the guide RNA, via viral vehicle, into the blood so that all cells in the brain would be subject to edit, and to discover side effects.
However, research also showed that the RNA approach resulted in the guide RNA editing places other than the MECP2 gene. No side effects were attributed to the off-target effects, but decreasing off-target edits and increasing editing efficiency is a top priority in future studies.