Oligonucleotide antiviral medications

Related Terms

Anticancer oligonucleotides, antisense DNA, antiviral oligonucleotides, cancer, fomivirsen, hepatitis virus, HIV, molecular therapy, oligonucleotide-based medicine, oligonucleotide antiviral medications, oligonucleotide therapy, RNA, RNA interference, RNAi, siRNA, virus, viral infection, Vitravene?.

Background

Antisense oligonucleotides are small molecules of genetic material designed to recognize and inactivate viral genes. In this way, oligonucleotides prevent viruses from replicating in the human body and can be used to treat viral infections. Oligonucleotides can also be used to prevent cancer cells from regenerating.
Genes are found inside the nucleus of cells in all organisms. Genes provide the instructions for making proteins in the body. An individual's genes are contained in a large molecule called DNA (deoxyribonucleic acid), which looks like a twisted ladder. This unique shape is called a double helix. The sides of the double helix are made of alternating sugar and phosphate molecules. The "rungs" of the "ladder" are made of small molecules called bases. These molecules include adenine, thymine, cytosine, and guanine. All genes are composed of different combinations of these four molecules, which are arranged in single file. The sequence of these molecules provides the "code," or instructions, for each of the genes involved in the development, growth, and function of all the cells in the body.
Humans have about 30,000 genes, each of which provides instructions for making a specific protein. Proteins are responsible for most of the chemical functions in the body. The genes, and a large amount of DNA that has other functions, are organized into molecules called chromosomes. Each person has 46 chromosomes, including 22 pairs of autosomes and one pair of sex chromosomes; males have one X and one Y chromosome, while females have two X chromosomes. The total genetic composition of an individual is called the human genome.
Ribonucleic acid (RNA) is composed of short molecules similar to and derived from DNA. Messenger RNA (mRNA) and transfer RNA (tRNA) complete the process of protein formation from the DNA code. RNA contains adenine, cytosine, and guanine like DNA, but instead of thymine it contains uracil.
Viruses also contain genetic material, but in much smaller amounts. The genetic material of viruses is different from that of humans because viruses can use DNA only or RNA only as their genetic material. When a virus infects a person, it multiplies and divides within human cells. Viruses use proteins of the human cell to "read" the viral DNA or RNA and produce viral proteins. Once the proteins are produced, they are assembled into new viruses that infect other cells.
Oligonucleotides are small segments of DNA or RNA. Unlike genes, which may be composed of hundreds or thousands of nitrogen bases, oligonucleotides are composed of about 20 nitrogen bases. Oligonucleotides can be specifically designed in a laboratory so that they bind to viral DNA or RNA. When an oligonucleotide binds to the viral DNA or RNA, it causes the genetic material to be inactive or destroyed.
In the treatment of cancer, oligonucleotide medicine attaches to the RNA in dividing cells and prevents them from continuing to multiply. Because cancer cells divide rapidly, oligonucleotide medicines prevent tumors from growing by inhibiting cell division.

Methods

Nucleotide sequencing: In order to create an oligonucleotide that binds to viral RNA, the specific sequence of the bases in the viral RNA must be determined. Nucleotide sequencing is a laboratory technique used to determine the sequence of bases within a segment of genetic material, in this case a piece of viral RNA.
Synthesis: Next, oligonucleotides are created from single nitrogen bases. The oligonucleotide is synthesized in an automated machine that adds the necessary nitrogen bases in the right amounts and at the right times. One end of the oligonucleotide is attached to a glass bead, and nitrogen bases are added to the other end through chemical reactions until the oligonucleotide is complete. Then, the extra nitrogen bases are washed off and the oligonucleotide is left attached to the glass bead. The addition of a chemical, commonly ammonia, causes the oligonucleotide to be released from the bead once it is ready to be used.
Administration: To be administered to humans, oligonucleotides are then packaged into an oral tablet or a solution for injection. There are different kinds of oligonucleotides. Antisense oligonucleotides are an exact mirror image of the viral RNA that it targets. Because it is a mirror image, the antisense oligonucleotide binds directly to the viral RNA, prevents it from functioning, and signals the cell to destroy it.
Vitravene? is an example of a currently available oligonucleotide. Vitravene? is an oligonucleotide that binds to the genetic material of a virus called cytomegalovirus to prevent it from reproducing. Vitravene? is currently used in the treatment of cytomegalovirus infections of the eye (retinitis), which occur in patients with HIV.
Another type of oligonucleotide therapy is called RNA interference (RNAi). This pathway involves a small segment of RNA, called microRNA (miRNA). The miRNA molecule binds to the viral RNA and signals it to be degraded or inactivated.

Research

Much research is now focused on creating more oligonucleotide antiviral medications because these molecules cause relatively few side effects compared to currently available antiviral medicines. Researchers are attempting to create oligonucleotide medications to treat HIV, herpes simplex virus, hepatitis B virus, hepatitis C virus, and influenza, among others.
Research is also being performed to develop antisense oligonucleotides to treat cancer. By developing oligonucleotides that specifically target RNA in cancer cells, researchers are attempting to create new drugs that are more effective than options now in use.

Implications

Oligonucleotide therapies may be able to treat viruses for which there is no current treatment. They may also be safer and have a lower risk of side effects than other therapies because they act on viral particles and not human cells.
The development of anticancer oligonucleotides may help treat and possibly even cure some types of cancer.

Limitations

There are only a few antiviral oligonucleotide drugs on the market. Clinical trials are being performed in a variety of cancer types.
Each oligonucleotide drug must be specifically designed for the virus it targets. This makes research and development a long and costly process.

Future research

Future research will focus on the development of oligonucleotide therapies for more viruses and many types of cancer. Many common viruses, such as hepatitis C (HCV) and HIV, cannot yet be cured. The development of antisense oligonucleotides that target HCV or HIV may one day allow patients with these infections to live longer, healthier lives. Currently, research is focused on determining the RNA sequences of interest in HCV and HIV particles and testing oligonucleotides that target these sequences in clinical trials.
Some potentially fatal viruses that are rare in the United States, such as the West Nile virus and Dengue fever, currently have no treatment. Researchers are working to create oligonucleotide therapies to treat these viruses.
Many different clinical trials are now evaluating the effectiveness of oligonucleotide medicine in cancer treatment. The hope is that oligonucleotides will prevent cancer cells from multiplying and may therefore be useful alone or in combination with other cancer treatments. Open clinical trials are studying brain, blood, and skin cancers.
Research will also continually be performed to determine the method of delivery with the greatest effect, and to create oligonucleotides with few or no side effects.

Author information

This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

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