Biotechnology - Yu.O. Sazykin 2006

General Biotechnology
Genomics and Proteomics
The Human Genome - Antisense Oligonucleotides

It is known that certain diseases—both hereditary and non-hereditary—may be associated not with the deficiency or defect of a specific protein, but conversely, with the overproduction of a normal, functionally active protein. This gives rise to the task of partially or completely suppressing The production of such a protein with varying degrees of Variability. In other words, it is necessary to selectively inhibit the expression of the Gene encoding this protein, or the gene of the enzyme involved in the post-translational modification of this protein and its conversion into the active form.

Accordingly, the concept was put forward for developing innovative therapeutics known collectively as antisense oligonucleotides. The underlying idea is to generate a nucleotide sequence complementary to the DNA of each gene (or a region thereof) which, through hydrogen bonding, will interact with the gene's DNA or with the Messenger RNA transcribed from that DNA.

In the first case, the suppression of excess protein production via binding to the gene occurs at the METABOLISM/31.html">Transcription stage, whereas In the second case (via binding to messenger RNA), it occurs at the Translation stage. The Specificity of the antisense nucleotide sequence—that is, the selectivity of action on the targeted gene—is achieved at a chain length of 15 to 20 NUCLEOTIDES (hence the term "oligonucleotides").

To put the idea of using antisense oligonucleotides as therapeutic agents into practice, several challenges must be overcome: solving Structure/149.html">The problem of targeted delivery to target Cells within The Human Body, and ensuring the protection of antisense oligonucleotides against degradation by Nucleases. Proposed solutions include: modifying these nucleotides within the respective drug formulations to hinder nuclease attack without interfering with their ability to bind to the target DNA or RNA; and "encapsulating" these nucleotides in Liposomes, among other approaches.