Gene Silencing Therapy

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Gene silencing is a natural process utilized by researchers to understand the role of particular genes in disease. It is used medically to cure and treat disease. How can it not be ethical?

Let's look at what is involved in the process known as gene silencing.

When a gene is turned off, it is silenced. There is no protein produced by that gene; its expression is zero. This is a natural process within cells depending on the tissue, conditions, and any mutations present in the sequence. Not all genes are on at the same time in every cells.

Cells accomplish gene silencing a number of ways: epigenetic changes such as DNA methylation, DNA-protein interactions (transcription silencing), and post-transcriptional silencing such as RNAi. What cells do is inherent in life and has no ethical realm. What is in question must be the use of these processes by humans.

Who uses gene silencing?

Experimentally, scientists use gene silencing to determine the role of a gene or mutation in the living organism and thus understand the etiology of disease. By silencing a gene in a cell culture or animal model, researchers can determine what processes are affected by the absence of the protein and in what way. If silencing the gene product results in no disease, then the presence of the gene product (i.e. expression of the gene) plays a role in that disease, indicating genes of interest for further study to determine treatments and cures for disease. The information is beyond genetics and DNA, but shows which proteins can be targeted by pharmaceuticals, injected, or targeted for faster breakdown within the body. Studying gene silencing helps scientists understand the complex, natural processes of gene expression and disease.

Doctors use gene silencing as a therapeutic approach to treating diseases caused by excess or unneeded gene expression. If doctors can silence the deranged gene, they can (theoretically) cure diseases. Interfering RNA (RNAi) is currently the subject of clinical trials for treating Huntington's Disease, some types of cancer, growth deficiencies, and as an antiviral therapy for hepatitis, among others.

Interfering RNA Treatment

RNAi the use of short single-stranded RNA sequences (siRNA) to target the mRNA of a gene and mark it for destruction by the cell's natural processes before it can be transcribed into protein. This is a natural process discovered in plants in 1999. The RNAi pathway is a feedback mechanism that shuts off genes using snippets of their own products. Enzymes clip the mRNA into short fragments that bind to full length mRNA being transcribed from the DNA. This targets the mRNA for destruction. In cell cultures, silencer sequences are produced synthetically that target particular human mRNA sequences, which are specific to a gene. There is also now a method for gene activation using double stranded RNA.

The RNAi pathway intersects with many pathways and can result in nonspecific effects. This risk has to be weighed with the benefits from therapy. Another risk is that the silenced gene affects another process beyond the disease being treated. Different RNAs are also variably effective in different types of cells.

In 2005, clinical trials showed that patients tolerate RNAi therapy well and that it could be a viable approach to treating HIV infection, among other diseases. However, a year later, questions about the safety of RNAi therapy were raised and it is still being studied as a possibility.

Any ethical questions about the use of gene silencing would include the risks of the therapy, which are being addressed and is important for each patient to decide on their own in conjunction with their doctor. As for the genetics of the procedure, it's all natural.

More about this author: Alicia M Prater PhD

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