The Genetic Code
Genes contain all the information needed to make or assemble proteins, which the body requires to function. Genes are made of DNA, which is comprised of 4 nucleotides. A nucleotide consists of a sugar molecule, deoxyribose in DNA or ribose in RNA attached to a phosphate group and a nitrogen containing base. The bases used in DNA are adenine (A), cytosine (C), guanine (G) and thymine (T). In RNA, the base uracil (U) takes the place of thymine. DNA and RNA molecules are polymers made up of long chains of nucleotides.
Gene expression begins with transcription, when a copy of the DNA that comprises the gene is made or transcribed into a messenger RNA (mRNA) which includes all of the information required to produce functional proteins. The single stranded mRNA can be made up of hundreds of nucleotides. The mRNA is read three nucleotides at a time, in units called codons, by a ribosome. There are 64 triplet codons for which 61 encode for amino acids and 3 encode for stop codons that terminate the translation process. The three stop codons are UGA, UAA, UAG. Proteins can be made up of hundreds of amino acids.
A nonsense mutation is a single point genetic mutation in a DNA sequence that when transcribed into mRNA results in changing an amino acid codon to a stop codon. When the mutated sequence is translated into a protein, the ribosome prematurely terminates at the stop or “nonsense” codon and results in shorter, incomplete protein, which is usually non-functional and rapidly degraded. Nonsense mutations are responsible for 10-15% of all inherited diseases, such as Duchenne muscular dystrophy.
PTC’s nonsense readthrough technology identifies small molecules that promote the insertion of an amino acid at the nonsense codon, thereby enabling the ribosome to readthrough this early stop signal. This results in the production of a full-length, functional protein. Using this technology, PTC identified Translarna™ (ataluren) for the treatment of nonsense mutation genetic disorders, including Duchenne muscular dystrophy.