Treatment of Nonsense Mutations Using Stop Codon Read-through Therapeutics and Creation of Animal Models Using CRISPR-Cas9

Copyright: © 2015 Turner KA, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Premature termination codons result when a mutation within a protein coding sequence causes an amino acid-encoding sense codon to be interpreted as a stop codon. Often, this results in truncation and destruction of the mRNA transcript or a non-functional protein. Nonsense mutations account for approximately 11 % of all described mutations that contribute to disease. A number of therapeutics, including suppressor tRNAs, gentamicin, and PTC124, have been developed that purport to promote the “read-through ” of these premature termination codons so that they are interpreted as sense codons. This, theoretically, would reconstitute the full-length transcript and restore protein/enzyme function and ameliorate disease symptoms. Currently, the implementation of such therapeutics in a clinical setting has been slow due to factors such as toxicity and inefficiency. We will discuss these hurdles as well as the difficulties associated with determination of the required protein/enzyme level to reduce symptoms as well as breakthroughs in genome editing to create nonsense mutation animal models using the clustered regularl