RNA Interface (RNAi)

In this article we will discuss about RNA Interface (RNAi):- 1. Subject Matter of RNAi 2. Advantages of RNAi 3. Disadvantages.

Subject Matter of RNAi:

RNA interference (RNAi) has emerged as an effective method to target specific genes for silencing. It is a naturally occurring mecha­nism that leads to the “silencing” of genes. In consequence, the respective protein is no longer synthesized(l). By nature, this mecha­nism is used for the regulation of specific genes and is also applied as a defense against viruses.

It was first experimentally documented in 1998 in Caenorhabditiselegans by Fire et al., who were later awarded the Nobel Prize in 2006 for his contribution to the fields of Physiology/Medicine. Subsequently RNAi studies have demonstrated the clinical potential of synthetic small interfering RNAs (siRNAs) or short hair­pin RNAs (shRNAs) in oral diseases, cardio­vascular diseases, ocular diseases, cancer, metabolic diseases, neurodegenerative disor­ders and many more.

RNAi holds a great prom­ise in the field of cancer therapy. In recent studies, the silencing of genes associated with cancer by RNAi technology has generated sig­nificant anti-proliferative effects in cell culture systems or in preclinical animal models.

Advantages of RNAi:

1. It is a natural pathway to gear up the crea­tion of new class of innovative medicines that can be further designed to be highly potent for treating variety of diseases.

2. RNAi is capable of targeting any given pro­tein thereby eliminating the key limitation of traditional medicines that can only tar­get certain classes of proteins.

3. It enables forthright identification of ap­propriate drug candidates using siRNAs that can be designed eventually to be ac­tive across a wide range of species.

4. It has the ability to selectively deplete a specific protein of interest in cultured cells using siRNAs, plasmids and viral vectors.

5. The timing and extent of the gene silenc­ing can be controlled. Hence, the essential genes can be silenced at any stages of growth and this approach provides a great degree of flexibility.

Disadvantages of RNAi:

1. The direct introduction of chemically syn­thesized siRNAs into the cells is limited by the short-lived nature of their transient gene silencing effects and their relative instability.

2. Though a high degree of specificity is as­sociated with RNAi yet some effects have been observed that are independent of the specific gene targeted for silencing.

3. Nucleic acid-based gene-silencing mol­ecules may have effects on genes that are not considered targets and these off-tar- get effects are due to similarities in nucleic acid sequences.

4. The specificity of RNAi-mediated degrada­tion of homologous mRNA makes this strategy highly prone to the development of resistance, as simple changes in target sequences may make previously effective siRNA triggers absolutely impotent.

5. The targeting of proteins with a long half- life may result in therapeutic failure de­spite successful gene silencing, since si­lencing at the transcript level does not af­fect pre-existing proteins.