The importance and effects of antisense oligos
INTRODUCTION
Conventional small-size molecule antiviral agents house enzymes that are essential to viral imitation or repeal transcription. The synthesis and design of antiviral agents based on nucleoside is proved to be effective and many clinically significant drugs have been developed using the same antiviral agents (e.g. acyclovir). However, there are significant difficulties in developing compounds with the capability to eliminate the viruses in entirety or to prevent their mixing up into the host genome. For this specific reason that there are a number of Oligonucleotide-based approaches are being developed to increase the effect.
ANTISENSE OLIGONUCLEOTIDES
For most part, viruses and bacteria have unique proteins that essentially help them to survive. The mRNA sequences that determine these proteins are not found in the human genome which makes it more difficult to eliminate the foreign mRNA molecules without interfering with the mRNA of the host is potentially of great therapeutic value. Furthermore, the progresses in DNA sequencing technology have made the information needed to target pathogen readily available. Antisense Oligonucleotides are designed to actually do this precise job. They hybridize to a particular mRNA and reduce expression of particular proteins.
If the protein which is in the question is important and essential for replication of a virus, or for unrestrained growth of cancer cells, a therapeutic effect maybe observed. However, in theory, antisense Oligonucleotides can be used to block the synthesis of protein in normal cells to stop the biological effect of specific proteins. But, in this application the earliest developed RNAi method is more acceptable.
The RNA: DNA combination duplex that is developed between antisense Oligonucleotideand the target mRNA meddles directly with protein synthesis which results in expression of coded protein. This difference is caused due to the inability of the ribosome to assemble around the mRNA when it is linked with the antisense Oligonucleotides and/or the inability of the hybrid to through the ribosome and direct protein expression. The effect of antisense is increased by the endonucleases activity of ribonucleause H (RNase H) on mRNA molecules that are hybridized to antisense Oligonucleotides. RNase H eliminates the mRNA strand, and both RNAse H enzyme but the antisense Oligonucleotide remains intact at the end of the cycle: the antisense effect is therefore catalytic. A single antisense Oligonucleotide can take part in the elimination of many mRNA molecules by this mechanism.
The enzyme RNase H which occurs in normal cells plays an important and helpful role in the removal of short pieces of RNA from the lagging strands of DNA replication. The human genome carries 3 × 109 base pairs. Therefore, statistically any DNA sequence of 17 bases or more will possibly occur only once or not at all (417 is greater than 1010). If a region of the mRNA of a viral protein is targeted with an antisense Oligonucleotide the Oligonucleotide should be selective for the viral mRNA. But in normal circumstances it is unfortunate that by simply adding chemically unmodified antisense Oligonucleotides to the cells in culture or to organism in vivo do not often results any significant antisense effect.
Conventional small-size molecule antiviral agents house enzymes that are essential to viral imitation or repeal transcription. The synthesis and design of antiviral agents based on nucleoside is proved to be effective and many clinically significant drugs have been developed using the same antiviral agents (e.g. acyclovir). However, there are significant difficulties in developing compounds with the capability to eliminate the viruses in entirety or to prevent their mixing up into the host genome. For this specific reason that there are a number of Oligonucleotide-based approaches are being developed to increase the effect.
ANTISENSE OLIGONUCLEOTIDES
For most part, viruses and bacteria have unique proteins that essentially help them to survive. The mRNA sequences that determine these proteins are not found in the human genome which makes it more difficult to eliminate the foreign mRNA molecules without interfering with the mRNA of the host is potentially of great therapeutic value. Furthermore, the progresses in DNA sequencing technology have made the information needed to target pathogen readily available. Antisense Oligonucleotides are designed to actually do this precise job. They hybridize to a particular mRNA and reduce expression of particular proteins.
If the protein which is in the question is important and essential for replication of a virus, or for unrestrained growth of cancer cells, a therapeutic effect maybe observed. However, in theory, antisense Oligonucleotides can be used to block the synthesis of protein in normal cells to stop the biological effect of specific proteins. But, in this application the earliest developed RNAi method is more acceptable.
The RNA: DNA combination duplex that is developed between antisense Oligonucleotideand the target mRNA meddles directly with protein synthesis which results in expression of coded protein. This difference is caused due to the inability of the ribosome to assemble around the mRNA when it is linked with the antisense Oligonucleotides and/or the inability of the hybrid to through the ribosome and direct protein expression. The effect of antisense is increased by the endonucleases activity of ribonucleause H (RNase H) on mRNA molecules that are hybridized to antisense Oligonucleotides. RNase H eliminates the mRNA strand, and both RNAse H enzyme but the antisense Oligonucleotide remains intact at the end of the cycle: the antisense effect is therefore catalytic. A single antisense Oligonucleotide can take part in the elimination of many mRNA molecules by this mechanism.
The enzyme RNase H which occurs in normal cells plays an important and helpful role in the removal of short pieces of RNA from the lagging strands of DNA replication. The human genome carries 3 × 109 base pairs. Therefore, statistically any DNA sequence of 17 bases or more will possibly occur only once or not at all (417 is greater than 1010). If a region of the mRNA of a viral protein is targeted with an antisense Oligonucleotide the Oligonucleotide should be selective for the viral mRNA. But in normal circumstances it is unfortunate that by simply adding chemically unmodified antisense Oligonucleotides to the cells in culture or to organism in vivo do not often results any significant antisense effect.
