New options for targeting gene mutation in FA described in nucleic acid therapeutics

March 8, 2018 by Kathryn Ryan, Mary Ann Liebert, Inc
Credit: Mary Ann Liebert, Inc., publishers

Researchers have shown that a wide variety of synthetic antisense oligonucleotides with different chemical modifications can activate the frataxin gene, which contains a mutation that decreases its expression in the inherited neurologic disorder Friedreich's ataxia (FA). This new finding, which demonstrates a broad range of flexible options for identifying novel compounds capable of increasing frataxin protein expression and alleviating the effects of FA, is published in Nucleic Acid Therapeutics.

The article entitled "Activation of Frataxin Protein Expression by Antisense Oligonucleotides Targeting the Mutant Expanded Repeat" is coauthored by David Corey UT Southwestern Medical Center at Dallas, TX and coauthors from Ionis Pharmaceuticals (Carlsbad, CA), McGill University (Montreal, Canada), and University of Massachusetts (Worcester, MA). The researchers show that various nucleic acid compounds with a range of chemical modifications are able to bind to the abnormal GAA repeat sequences in the FA gene. They demonstrated this in multiple cell lines derived from FA patients who had varied numbers of GAA repeats, implying a strong foundation for future drug development.

"The resources and long-term commitment required to pursue these types of investigations underline the needs and benefits of academia-industry collaborations that are advancing the field," says Executive Editor Graham C. Parker, PhD, The Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Children's Hospital of Michigan, Detroit, MI.

Research reported in this publication was supported by the National Institutes of Health under Award Number GM R35118103. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Explore further: Unraveling the mechanism of antisense oligonucleotides

More information: Liande Li et al, Activation of Frataxin Protein Expression by Antisense Oligonucleotides Targeting the Mutant Expanded Repeat, Nucleic Acid Therapeutics (2018). DOI: 10.1089/nat.2017.0703

Related Stories

Unraveling the mechanism of antisense oligonucleotides

February 2, 2017
Stanley T. Crooke, MD, PhD, CEO of Ionis Pharmaceuticals and recipient of the 2016 Lifetime Achievement Award from the Oligonucleotide Therapeutic Society presents a detailed look at the mechanisms that underlie antisense ...

New method stabilizes siRNAs without affecting gene silencing activity

January 9, 2018
Researchers have reported the ability to modify the structure of small interfering RNAs (siRNAs) to improve their stability and therapeutic potential without negatively affecting their potency and ability to silence targeted ...

Scientists find potential treatment for Friedreich's ataxia

February 16, 2016
Researchers at UT Southwestern Medical Center have identified synthetic RNA and DNA that reverses the protein deficiency causing Friedreich's ataxia, a neurological disease for which there is currently no cure.

New study shows a breadth of antisense drug activity across many different organs

December 11, 2013
Antisense therapeutics, a class of drugs comprised of short nucleic acid sequences, can target a dysfunctional gene and silence its activity. A new study has shown that antisense drugs delivered systemically show activity ...

Modified DNA backbone enables success of existing and novel oligonucleotide therapeutics

November 13, 2014
The two U.S. FDA approved oligonucleotide-based drugs on the market both have a modified chemical backbone made of phosphorothioates. The therapeutic advantages of the phosphorothioate group and the new types of gene expression-regulation ...

More potent, inexpensive gene silencing agents described

May 12, 2016
Combining the therapeutic potential and advantages of existing oligonucleotide-based approaches to turn off disease-related genes, a type of single-stranded silencing RNAs (ss-siRNAs) has shown significantly improved potency ...

Recommended for you

A new approach to developing a vaccine against vivax malaria

September 21, 2018
A novel study reports an innovative approach for developing a vaccine against Plasmodium vivax, the most prevalent human malaria parasite outside sub-Saharan Africa. The study led by Hernando A. del Portillo and Carmen Fernandez-Becerra, ...

Study identifies stem cell that gives rise to new bone and cartilage in humans

September 20, 2018
A decade-long effort led by Stanford University School of Medicine scientists has been rewarded with the identification of the human skeletal stem cell.

Scientists grow human esophagus in lab

September 20, 2018
Scientists working to bioengineer the entire human gastrointestinal system in a laboratory now report using pluripotent stem cells to grow human esophageal organoids.

Researchers identify human skeletal stem cells

September 20, 2018
Human skeletal stem cells that become bone, cartilage, or stroma cells have been isolated from fetal and adult bones. This is the first time that skeletal stem cells, which had been observed in rodent models, have been identified ...

A new app enables a smartphone to ID bacteria in just one hour

September 20, 2018
In a potential game changer for the health care industry, a new cell phone app and lab kit now allow a smartphone to identify bacteria from patients anywhere in the world. With the new app, doctors will be able to diagnose ...

Synthetic sandalwood found to prolong human hair growth

September 19, 2018
A team of researchers led by Ralf Paus of the University of Manchester has found that applying sandalwood to the scalp can prolong human hair growth. In their paper published in the journal Nature Communications, the group ...

0 comments

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.