Team overrides faulty genetic signalling for first time

Posted by Kate Taylor

Scientists have discovered an entirely new way to change the genetic code, bringing hope of treatments for devastating genetic disorders such as cystic fibrosis, muscular dystrophy and many forms of cancer.

The genetic code is the set of instructions in a gene that tell a cell how to make a specific protein. Central to the body’s protein production process is messenger RNA, or mRNA, which takes these instructions from DNA and directs the steps necessary to build a protein.

For the first time, researchers artificially modified messenger RNA - which takes instructions from DNA and directs the building of proteins, changing the original instructions to create a different protein.

"The ability to manipulate the production of a protein from a particular gene is the new miracle of modern medicine," says Robert Bambara chair of the Department of Biochemistry and Biophysics at the University of Rochester Medical Center.

"This is a really powerful concept that can be used to try to suppress the tendency of individuals to get certain debilitating, and sometimes fatal genetic diseases that will forever change their lives."

The researchers focused on a common type of mutation that occurs when an mRNA molecule contains a premature 'stop' signal, known as a pre-mature stop codon. This orders a cell to stop reading the genetic instructions partway through the process, resulting in the creation of an incomplete, shortened protein. 

And the team was able to alter mRNA so that the 'stop' signal turned into 'go'. As a result, the cell could read the genetic instructions all the way through and create a normal, full-length protein. The team produced the results both in vitro and in live yeast cells.

Around a third of genetic diseases are believed to be caused by the presence of these premature stop codons  - meaning the technique could lead to treatments for diseases such as cystic fibrosis and some types of cancer.

"Previous research has presented other ways to modify the genetic code, but what is really unique about our method is that it is at the RNA level and it is site specific," says study lead author Yi-Tao Yu.

"We can express the artificial guide RNA in a cell and direct it to make a modification at a single site and only that site."