Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gene therapy: Editing out genetic damage

01.02.2013
New design guidelines from researchers in Singapore simplify the development of targeted therapies for muscular dystrophy and other diseases
The dystrophin protein offers critical support to muscle fibers. Mutations affecting dystrophin’s expression cause the muscle-wasting disease muscular dystrophy. In Duchenne muscular dystrophy (DMD), these mutations take the form of small sequence changes that make much of the dystrophin gene (DMD) untranslatable, yielding nonfunctional protein or no protein at all.

Therapies based on a strategy known as ‘exon skipping’ could undo the damage from these mutations. Development of such treatments is set to accelerate, thanks to research by a team led by Keng Boon Wee of the A*STAR Institute of High Performance Computing and Zacharias Pramono of the National Skin Centre in Singapore1.

Proteins are translated from messenger RNA transcripts of genes; however, only certain RNA regions - known as exons - actually encode protein, and these are enzymatically spliced together prior to translation. Several clinical studies have demonstrated that small ‘antisense oligonucleotide’ (AON) molecules that bind mutated DMD exons can induce elimination of those defective exons during splicing, yielding shorter but largely functional versions of dystrophin. “We are cautiously optimistic that AON-induced exon skipping could be the first effective therapy for DMD patients,” says Wee.

Unfortunately, DMD arises from many different mutations, and targeted AON design remains a time-consuming, trial-and-error process. To address this challenge, Wee and Pramono sought to define the characteristics of AONs that efficiently promote exon-skipping. They used computational analysis to zoom in on exonic sequences that coordinate splicing. They also identified regions of suitable length within dystrophin RNA transcripts that span these sequences and would be accessible to AONs in living cells.

The researchers thus derived a set of guidelines enabling them to effectively design AONs that targeted nine different exons affected in DMD patients. For each exon, at least one AON proved capable of boosting dystrophin expression to clinically relevant thresholds in cultured muscle cells (see image). “Our proposed set of factors resulted in a reasonable success rate of designing efficient AONs - 61% versus 38% using semi-empirical methods,” says Wee. Clinical studies have already demonstrated the promise of efficient exon skipping in treating DMD patients.

Wee notes that other diseases arising from abnormal RNA processing could also benefit from this approach. However, his team is also exploring this method as a general strategy to abort production of disease-causing proteins in cancer and other conditions. “In contrast to small-molecule inhibitor drugs that can target only about 10% of the human genome, this approach could downregulate most human genes,” Wee says.

The A*STAR-affiliated researchers contributing to this research are from the Institute of High Performance Computing
Associated links
http://www.research.a-star.edu.sg/research/6621
Journal information
Pramono, Z. A. D., Wee, K. B., Wang, J. L., Chen, Y. J., Xiong, Q. B. et al. A prospective study in the rational design of efficient antisense oligonucleotides for exon skipping in the DMD gene. Human Gene Therapy 23, 781–790 (2012).

A*STAR Research | Research asia research news
Further information:
http://www.research.a-star.edu.sg/research/6621
http://www.researchsea.com

More articles from Life Sciences:

nachricht Fruit fly studies shed light on adaptability of nerve cells
17.04.2015 | Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. (DZNE)

nachricht Rare monkey photographed in Congo's newest national park, Ntokou-Pikounda
17.04.2015 | Wildlife Conservation Society

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Astronomers reveal supermassive black hole's intense magnetic field

Astronomers from Chalmers University of Technology have used the giant telescope Alma to reveal an extremely powerful magnetic field very close to a supermassive black hole in a distant galaxy

Astronomers from Chalmers University of Technology have used the giant telescope Alma to reveal an extremely powerful magnetic field very close to a...

Im Focus: A “pin ball machine” for atoms and photons

A team of physicists from MPQ, Caltech, and ICFO proposes the combination of nano-photonics with ultracold atoms for simulating quantum many-body systems and creating new states of matter.

Ultracold atoms in the so-called optical lattices, that are generated by crosswise superposition of laser beams, have been proven to be one of the most...

Im Focus: UV light robot to clean hospital rooms could help stop spread of 'superbugs'

Can a robot clean a hospital room just as well as a person?

According to new research out of the Texas A&M Health Science Center College of Medicine, that is indeed the case. Chetan Jinadatha, M.D., M.P.H., assistant...

Im Focus: Graphene pushes the speed limit of light-to-electricity conversion

Researchers from ICFO, MIT and UC Riverside have been able to develop a graphene-based photodetector capable of converting absorbed light into an electrical voltage at ultrafast timescales

The efficient conversion of light into electricity plays a crucial role in many technologies, ranging from cameras to solar cells.

Im Focus: Study shows novel pattern of electrical charge movement through DNA

Electrical charges not only move through wires, they also travel along lengths of DNA, the molecule of life. The property is known as charge transport.

In a new study appearing in the journal Nature Chemistry, authors, Limin Xiang, Julio Palma, Christopher Bruot and others at Arizona State University's...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

HHL's Entrepreneurship Conference on FinTech

13.04.2015 | Event News

World Conference On Regenerative Medicine 2015: Registration And Abstract Submission Now Open

25.03.2015 | Event News

University presidents from all over the world meet in Hamburg

19.03.2015 | Event News

 
Latest News

Engineer Improves Rechargeable Batteries with MoS2 Nano 'Sandwich'

17.04.2015 | Power and Electrical Engineering

Comparing Climate Models to Real World Shows Differences in Precipitation Intensity

17.04.2015 | Earth Sciences

A blueprint for clearing the skies of space debris

17.04.2015 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>