The RNA drug revolution -- a new approach to gene therapy

January 23, 2008

RNA interference (RNAi) represents an innovative new strategy for using small RNA molecules to silence specific genes associated with disease processes, and a series of review articles describing the state-of-the-art and potential therapeutic applications of RNAi and microRNAs will begin with two review papers in the January 2008 issue (Volume 19, Number 1) of Human Gene Therapy, a peer-reviewed journal published by Mary Ann Liebert, Inc. The papers are available free online.

At least six clinical trials using RNA interference (RNAi) have been approved, “with many more coming down the pipeline,” according to the Editorial by Mark A. Kay, MD, PhD, an Associate Editor of Human Gene Therapy and the Dennis Farrey Family Professor in Pediatrics and Professor of Genetics at Stanford University School of Medicine. “One thing is clear,” adds Kay, “small RNAs as a therapeutic platform are here to stay.”

The excitement surrounding RNAi and the two main approaches to delivering RNA-based therapeutics—as mature siRNA molecules or as short hairpin RNAs (shRNAs)—relates to the discovery of native microRNA molecules in human cells and their intrinsic ability to block the expression of a target gene. siRNA therapeutic strategies in development aim to harness the cells’ natural RNAi pathway and specifically silence a mutant or dysregulated gene.

Traditionally, gene therapy has focused on supplying a normal copy of a faulty gene, whereas RNAi turns off a problematic gene. These contrasting approaches share some of the same techniques and challenges, including delivery of a therapeutic gene or siRNA into cells.

Human Gene Therapy will publish a series of review papers in four consecutive issues focusing on a range of topics related to therapeutic applications of small RNAs. The series begins in the January issue with a paper entitled, “Behind the Scenes of a Small RNA Gene-Silencing Pathway,” by Gregory Ku, MD, PhD, and Michael McManus, PhD, from the University of California, San Francisco, which presents the current understanding of microRNA mechanisms of action and the potential for applying this knowledge to the development of RNAi-based treatments.

In the review by Anton McCaffrey, PhD, and Rebecca Marquez, MA, entitled, “Advances in Micro-RNAs: Implications for Gene Therapists,” the authors discuss the likelihood that microRNAs, which are believed to regulate as many as one-third of all human gene transcripts (or messenger RNAs), are implicated in many human diseases. Using gene therapy to manipulate microRNA levels represents an attractive new approach for controlling gene expression and identifying targeted and effective therapeutics.

"The concept of using RNA as a therapeutic product is quite attractive and adds an important new dimension to the field of nucleic acid based therapeutics including gene therapy. Mark Kay, Associate Editor of Human Gene Therapy, has organized an exciting series of reviews summarizing the state of the art of this emerging field," says James M. Wilson, MD, PhD, Editor-in-Chief, and Head of the Gene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, in Philadelphia.

Source: Mary Ann Liebert, Inc.

Explore further: Scientists reveal how stem cells defend against viruses

Related Stories

Scientists reveal how stem cells defend against viruses

September 21, 2015

Scientists from the Institute of Molecular and Cell Biology (IMCB), a research institute under the Agency for Science, Technology and Research (A*STAR), Singapore, have uncovered the mechanisms which embryonic stem cells ...

Making nanowires from protein and DNA

September 3, 2015

The ability to custom design biological materials such as protein and DNA opens up technological possibilities that were unimaginable just a few decades ago. For example, synthetic structures made of DNA could one day be ...

Clever feedback system regulates immune responses

August 17, 2015

A newly discovered feedback mechanism in the body is responsible for keeping immune responses from getting out of hand. It works at the level of certain genes, linking the inactivation of those genes to the progress made ...

Recommended for you

How the finch changes its tune

August 3, 2015

Like top musicians, songbirds train from a young age to weed out errors and trim variability from their songs, ultimately becoming consistent and reliable performers. But as with human musicians, even the best are not machines. ...

Machine Translates Thoughts into Speech in Real Time

December 21, 2009

( -- By implanting an electrode into the brain of a person with locked-in syndrome, scientists have demonstrated how to wirelessly transmit neural signals to a speech synthesizer. The "thought-to-speech" process ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

not rated yet Jan 28, 2008
Microarrays (gene chips) can examine gene expression in up to 50,000 different genes at once. It's mainly used for screening/gene discovery work. You screen 50,000 genes to discover an association and then you focus in on only a few hundred or so for more careful study by some other method. The "gold standard" for sensitivity and reproducibility is called real time polymerase chain reaction, or RT-PCR.

Genes make proteins, the molecules that comprise and maintain all the body's tissues. Genes produce their effect by sending molecules called messenger RNA to the protein-making machinery of a cell. They set the protein-making machinery in motion through a "gofer" messenger called RNA (or mRNA).

The technique called RNA interference (RNA-i) allows scientists to "silence" certain genes. In RNA interference, certain molecules trigger the destruction of RNA from a particular gene, so that no protein is produced. Thus, the gene is effectively silenced. RNA interference is already being widely used in basic science as a method to study the function of genes and it is being studied as a treatment for infections such as cancer.

RNA interference occurs naturally in plants, animals, and humans. RNA interference is important for regulating the activity of genes (a fundamental mechanism for controlling the flow of genetic information). RNA interference (RNAi) interferes with mRNA, a natural molecular switch, regulating gene expression in plants, animals and humans, by "silencing" over-active or malfunctioning genes.

The ability to transfect (introducing foreign DNA into a cell) cultured cells with DNA gene sequences has allowed us to assign functions to different genes and understand the mechanisms that activate or redress their function. It has made gene therapy and stem cell research possible.

Cell culture technology has revived many previously unattainable ambitions in medical science, including the Nobel prize winning discovery of RNA interference. Tissue culture methods have played a major part in the work of more than a third of the winners of the Nobel prize for medicine since 1953.

The key to understanding the genome is understanding how cells work. The ultimate driver is "functional" assay analysis (is the cell being killed regardless of the mechanism) as opposed to a "target" assay (does the cell express a particular target that the drug is supposed to be attacking). While a "target" assay tells you whether or not to give one drug, a "functional" assay can find other compounds and combinations and can recommend them from the one assay.

The core of the "functional" assay is the cell, composed of hundreds of complex molecules that regulate the pathways necessary for vital cellular functions. If a "targeted" drug could perturb any one of these pathways, it is important to examine the effects of the drug within the context of the cell. Both genomics and proteomics can identify potential new therapeutic "targets," but these "targets" require the determination of cellular endpoints.

Cell-based "functional" assays are being used for screening compounds for efficacy and biosafety. The ability to track the behavior of cancer cells permits data gathering on "functional" behavior not available in any other kind of assays.

Source: Cell Function Analysis

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.