Delta Scan: The Future of Science and Technology, 2005-2055: Therapeutic and Research Uses of RNA Interference

Key Pages

Category:
Science and Technology

Domain:
Biology and Biotechnology

Keywords:
Biotechnology & genetics - cell biology, molecular biology, RNA, biotechnology, therapeutics, genetically modified organisms, gene silencing

Outlook:
New discoveries by cell biologists regarding the role of RNA in gene regulation have provided researchers with a powerful tool that will likely have wide-ranging impact. These discoveries have also spurred the formation of biotechnology companies aiming to develop RNA-based therapies.

Summary Analysis:
Research on RNA, the intermediary messenger molecule between DNA and protein synthesis, has long been of secondary interest compared to DNA. Discoveries in the last decade, however, have shown RNA to have a complex role in gene regulation. An especially significant discovery is that some kinds of RNA can interfere with gene expression after translation from DNA. This phenomenon of RNA interference causing 'gene silencing' is leading to a fundamental revision of the understanding of the role of RNA. In the next decade, researchers will continue to sort out the function of RNA. The research is likely to have a significant impact on models of the cell and theories about genetic regulation and inheritance, specifically by challenging the notion of the exclusive power of DNA. Researchers hypothesize that the newly discovered property of what is now called small interfering RNA (siRNA) may be to protect the cell from viruses and provide a way of achieving genomic stability. The molecule may also play a role in development, perhaps offering a way to better understand stem cells. Of perhaps even greater consequence is that scientists have already learned to harness this natural genetic machinery to experimentally 'silence' the expression of specific genes.

The implications of this biological tool for new therapeutic strategies, as well as new genetically modified organisms, are being explored by the biotechnology industry with intense interest. Some new biotechnology companies have formed primarily around the concept of developing RNA-based therapies. Notwithstanding the industry investments, some critics believe that effective clinical applications of this new discovery may be decades away at best and point to past clinical disappointments with antisense RNA therapies, which were meant to treat genetic disorders by deactivating messenger RNA from a particular gene. Furthermore, the potential therapeutic benefits are likely to be costly and difficult to administer, suggesting wealthy countries and individuals stand to benefit the most initially.

Implications:

Fundamental revision of models of the cell and theories about gene regulation and inheritance
Realignment of research interests in molecular biology to focus on fruitful new areas
Advancement of molecular biology research and biotechnology as a result of having a research tool to silence specific genes
Potential for novel forms of disease treatment

Early Indicators:

The journal Science's naming of the discovery of RNA interference as 'breakthrough of the year' in 2002
Acuity Pharmaceutical's filing with the US Food and Drug Administration in August 2004 of a new investigational drug application involving the therapeutic use of RNA interference

What to Watch:

Commercial 'gene silencing' kits for research become available.
Results of long-term clinical trials show the efficacy of RNA-based therapies for age-related macular degeneration.
A Nobel Prize is awarded for research on the mechanics of RNA interference and downgrading of DNA as the 'master molecule'.

Parallels/Precedents:

Research on antisense RNA and interferon, leading to hopes for treatment of genetic diseases
Discovery of retroviruses, setting the stage for the biotechnology revolution

Enablers/Drivers:

Dissemination of research protocols to expand the use of RNA interference as a research tool
Investment from biotechnology companies to expand the range of potential clinical applications

Leaders:
Institutions:

Acuity Pharmaceuticals (testing of a treatment for age-related macular degeneration or AMD)
Alnylam Pharmaceuticals (developing therapies for AMD and respiratory syncytial virus infection)
Ribopharma (developing therapies for cancer and viral diseases)
Sirna Therapeutics (developing therapies for AMD, hepatitis C, asthma, and cancer)
Cenix Biosciences (provision of RNA interference research services)
Benitec, Australia (multiple gene-crippling to treat Type 2 Diabetes)[link]
IC-VEC, UK (developing therapies for Hepatitis B and C, liver diseases and cancer) [link]
RNAi Co, Japan [link]
Imperial College Genetic Therapies Centre, London [link]
The Wellcome Trust Sanger Institute [link]
The Wellcome Trust/Cancer Research UK Gurdon Institute of Cancer and Developmental Biology [link]
CSIRO, Australia [link]

Figures:

Sources:

Matzke, Marjori A. and Antonius J. Matzke. "Planting the Seeds of a New Paradigm." PLoS Biology 2, no. 5 (2004): E133.
Lau, Nelson C., and David P. Bartel. "Censors of the Genome." Scientific American 289, no. 2 (2003): 34-41.
Kloc, M., N. R. Zearfoss, and L. D. Etkin. "Mechanisms of Subcellular mRNA Localization." Cell 108, no. 4 (2002): 533-44.
Pollack, Andrew. "Method to Turn Off Bad Genes Is Set for Tests on Human Eyes." New York Times, September 14 2004, 1.
Robinson, Richard. "RNAi Therapeutics: How Likely, How Soon?" PLoS Biology 2, no. 1 (2004): E28.
Couzin, J. "Breakthrough of the Year. Small RNAs Make Big Splash." Science 298, no. 5602 (2002): 2296-7.
"RNA Interference and Gene Silencing: History and Overview." Ambion, The RNA Company [link]
Fire A. et al. "Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans." Nature 1998. 391: 806-11 [link]
Hannon, G. and Rossi, J. "Unlocking the potential of the human genome with RNA interference." Nature. September 16 2004. [link]
Downward, J. Cancer Research Institute. "RNA Interference." British Medical Journal. May 22 2004 [link]
"Silencing is Golden." [link] and "The Big Turn-Off: RNAi goes Clinical." [link] Wellcome Trust website, UK.

At A Glance:
When:
3-10 yrs

Where:
Global

How Fast:
Years

Likelihood:
Medium-High

Impact:
Medium-High

Controversy:
Low

Related Outlooks:

About this outlook: An outlook is an internally consistent, plausible view of the future based on the best expertise available. It is not a prediction of the future. The AT-A-GLANCE ratings suggest the scope, scale, and uncertainty associated with this outlook. Each outlook is also a working document, with contributors adding comments and edits to improve the forecast over time. Please see the revision history for earlier versions.

Category:	Science and Technology
Domain:	Biology and Biotechnology
Keywords:	Biotechnology & genetics - cell biology, molecular biology, RNA, biotechnology, therapeutics, genetically modified organisms, gene silencing
Outlook:	New discoveries by cell biologists regarding the role of RNA in gene regulation have provided researchers with a powerful tool that will likely have wide-ranging impact. These discoveries have also spurred the formation of biotechnology companies aiming to develop RNA-based therapies.
Summary Analysis:	Research on RNA, the intermediary messenger molecule between DNA and protein synthesis, has long been of secondary interest compared to DNA. Discoveries in the last decade, however, have shown RNA to have a complex role in gene regulation. An especially significant discovery is that some kinds of RNA can interfere with gene expression after translation from DNA. This phenomenon of RNA interference causing 'gene silencing' is leading to a fundamental revision of the understanding of the role of RNA. In the next decade, researchers will continue to sort out the function of RNA. The research is likely to have a significant impact on models of the cell and theories about genetic regulation and inheritance, specifically by challenging the notion of the exclusive power of DNA. Researchers hypothesize that the newly discovered property of what is now called small interfering RNA (siRNA) may be to protect the cell from viruses and provide a way of achieving genomic stability. The molecule may also play a role in development, perhaps offering a way to better understand stem cells. Of perhaps even greater consequence is that scientists have already learned to harness this natural genetic machinery to experimentally 'silence' the expression of specific genes. The implications of this biological tool for new therapeutic strategies, as well as new genetically modified organisms, are being explored by the biotechnology industry with intense interest. Some new biotechnology companies have formed primarily around the concept of developing RNA-based therapies. Notwithstanding the industry investments, some critics believe that effective clinical applications of this new discovery may be decades away at best and point to past clinical disappointments with antisense RNA therapies, which were meant to treat genetic disorders by deactivating messenger RNA from a particular gene. Furthermore, the potential therapeutic benefits are likely to be costly and difficult to administer, suggesting wealthy countries and individuals stand to benefit the most initially.

	Implications:	Fundamental revision of models of the cell and theories about gene regulation and inheritance Realignment of research interests in molecular biology to focus on fruitful new areas Advancement of molecular biology research and biotechnology as a result of having a research tool to silence specific genes Potential for novel forms of disease treatment
	Early Indicators:	The journal Science's naming of the discovery of RNA interference as 'breakthrough of the year' in 2002 Acuity Pharmaceutical's filing with the US Food and Drug Administration in August 2004 of a new investigational drug application involving the therapeutic use of RNA interference
	What to Watch:	Commercial 'gene silencing' kits for research become available. Results of long-term clinical trials show the efficacy of RNA-based therapies for age-related macular degeneration. A Nobel Prize is awarded for research on the mechanics of RNA interference and downgrading of DNA as the 'master molecule'.
	Parallels/Precedents:	Research on antisense RNA and interferon, leading to hopes for treatment of genetic diseases Discovery of retroviruses, setting the stage for the biotechnology revolution
	Enablers/Drivers:	Dissemination of research protocols to expand the use of RNA interference as a research tool Investment from biotechnology companies to expand the range of potential clinical applications
	Leaders:	Institutions: Acuity Pharmaceuticals (testing of a treatment for age-related macular degeneration or AMD) Alnylam Pharmaceuticals (developing therapies for AMD and respiratory syncytial virus infection) Ribopharma (developing therapies for cancer and viral diseases) Sirna Therapeutics (developing therapies for AMD, hepatitis C, asthma, and cancer) Cenix Biosciences (provision of RNA interference research services) Benitec, Australia (multiple gene-crippling to treat Type 2 Diabetes)[link] IC-VEC, UK (developing therapies for Hepatitis B and C, liver diseases and cancer) [link] RNAi Co, Japan [link] Imperial College Genetic Therapies Centre, London [link] The Wellcome Trust Sanger Institute [link] The Wellcome Trust/Cancer Research UK Gurdon Institute of Cancer and Developmental Biology [link] CSIRO, Australia [link]
	Figures:
	Sources:	Matzke, Marjori A. and Antonius J. Matzke. "Planting the Seeds of a New Paradigm." PLoS Biology 2, no. 5 (2004): E133. Lau, Nelson C., and David P. Bartel. "Censors of the Genome." Scientific American 289, no. 2 (2003): 34-41. Kloc, M., N. R. Zearfoss, and L. D. Etkin. "Mechanisms of Subcellular mRNA Localization." Cell 108, no. 4 (2002): 533-44. Pollack, Andrew. "Method to Turn Off Bad Genes Is Set for Tests on Human Eyes." New York Times, September 14 2004, 1. Robinson, Richard. "RNAi Therapeutics: How Likely, How Soon?" PLoS Biology 2, no. 1 (2004): E28. Couzin, J. "Breakthrough of the Year. Small RNAs Make Big Splash." Science 298, no. 5602 (2002): 2296-7. "RNA Interference and Gene Silencing: History and Overview." Ambion, The RNA Company [link] Fire A. et al. "Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans." Nature 1998. 391: 806-11 [link] Hannon, G. and Rossi, J. "Unlocking the potential of the human genome with RNA interference." Nature. September 16 2004. [link] Downward, J. Cancer Research Institute. "RNA Interference." British Medical Journal. May 22 2004 [link] "Silencing is Golden." [link] and "The Big Turn-Off: RNAi goes Clinical." [link] Wellcome Trust website, UK.

At A Glance:	When:	3-10 yrs
	Where:	Global
	How Fast:	Years
	Likelihood:	Medium-High
	Impact:	Medium-High
	Controversy:	Low