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The Theory Behind Antisense Oligonucleotide Therapy

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As you are probably aware, antisense oligonucleotides are synthetic single-stranded chains  of nucleic acids that bind to RNA (ribonucleic  acid) ; and in doing so alter the  or reduce the expression of the target RNA.  They reduce expression of mutant proteins and restore expression of wild type proteins. Anti-sense oligonucleotides also are known to interfere with pre-mRNA splicing.  In eukaryotic cells,  the double-stranded DNA templates are housed in the nucleus of the cell.  The twenty or so oncogenes (which are genes that are found in human DNA which can predispose a human being to various types of cancer) are flanked by five- prime and three-prime DNA sequences which render the the oncogene genome unable to express cancer-causing genes.  However, if a frame-shift or some other type of mutation occurs, the  messenger RNA that is transcribed from one of the template strands of DNA in the nucleus may intermediate the translation of cancer causing proteins (as this mRNA will find it’s way to the rough endoplasmic reticulum and be read by the anti-codons of tRNA), causing sequential amino acids to form protins by peptide linkages and ultimately lead to a cancerous condition.

One way to stop this so called activation of oncogenes from their so called proto-oncogenes  could be by flooding the cells with RNA sequences which would bind out the transcripts  that would ultimately find the ribosomes of the rough endoplasmic reticulum  and provide sequences for the anti-codon regions of the transfer RNAs (which form peptide linkages to the various amino acids on the opposite termini).

Antisense oligonucleotides are sometimes able to cross the blood brain barrier  by simple diffusion.  Another mechanism by which antisense oligonucleotides can cross the blood brain barrier is by the saturable oligonucleotide transport system. Additionally, a third mechanism which  allows the antisense oligonucleotides to cross the blood brain barrier  is via receptor mediated endocytosis.

Antisense oligonucleotide  mediated reduction of disease-specific upregulated proteins is now a potential treatment for  multiple sclerosis (MS).  MS is an autoimmune disease of the central nervous system (CNS) in which multifocal infiltration of autoreactive T lymphocytes across the blood brain barrier takes place.

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