The basics: Genes contain the building blocks to produce proteins. Proteins are essential components found in living cells, and they play different roles which are important in helping cells survive and function properly. In some cases certain proteins are abnormal (because of incorrect or over production) which can lead to human diseases. Antisense technology aims to stop production of these proteins, and therefore have a therapeutic effect in patients.
How are proteins made? Genes are made up of different bases or nucleotides called Adenine (A), Thymine (T), Cytosine (C) and Guanine (G), which pair together to form deoxyribonucleic acid (DNA). Double-stranded DNA is made up of complementary nucleotides, where C hybridizes to G (C-G) and A-T, and this complementary pairing is what holds the two strands of DNA together. One of these strands is called the ‘sense’ strand, and the other the ‘antisense’ strand. Proteins are made from DNA in two steps-transcription (1) and translation (2). In the first step, the two stands of DNA are separated, and the ‘sense’ strand, is used to recruit RNA molecules. RNA is just like DNA, however Thymine (T) is substituted by Uracil (U). The recruited RNA molecules form a strand that eventually encodes the messenger RNA (mRNA). The mRNA then associates with the ribosome in the cell, which then recruits the amino acids required to make up proteins.
What are antisense oligonucleotides? Antisense technology aims to bind to specific messenger RNA and stop targeted proteins being produced. Antisense oligonucleotides are short chemically modified strands of nucleotides that bind to specific complementary nucleotides found in the messenger RNA. In many cases when the antisense oligonucleotide or antisense drug binds to its complementary strand, it results in degradation of the mRNA, which means the targeted protein cannot be produced. Therefore the overall amount of the targeted protein in the cell will be reduced. This is the case for our Dyn-101 program. There are many different mechanisms by which antisense drugs can work (such as exon skipping, splice switching approaches), however the overall goal is normally to target reduction of the specific proteins causing disease. For patients in which the targeted proteins are over produced or abnormal, antisense drugs can have a strong therapeutic effect.