Synthetic Proteins for Muscular Dystrophy Treatment

Technology #16207

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John A. Berglund
Melissa Hale
Managed By
April Kilburn
Assistant Director 352-392-8929
Patent Protection
PCT Patent Application WO2017/214459

Displace or Replace Mutant MBNL Proteins that Cause Repeat Expansion Diseases

This synthetic muscleblind-like (MBNL) protein can displace or replace the mutations that cause repeat expansion diseases, such as myotonic muscular dystrophy and spinocerebellar ataxia. Repeat expansion mutations cause more than 20 types of neurological diseases, including myotonic muscular dystrophy types 1 and 2, Fuchs endothelial corneal dystrophy and spinocerebellar ataxia type 8. These diseases cause muscular and skeletal deterioration and often result in breathing and swallowing weakness, heart difficulties, and severe pain. Available treatments for these diseases only reduce the severity of symptoms. Researchers at the University of Florida have developed synthetic MBNL proteins for treating repeat expansion diseases that involve sequestration of MBNL proteins by toxic RNA. These synthetic compositions compensate for proteins that get depleted by the repeat expansion mutation and rescue disease-like phenotypes at lower concentrations compared to wild-type MBNL proteins.


Synthetic protein to treat repeat expansion diseases that involve sequestration of MBNL proteins


  • Demonstrates improved RNA binding properties and splicing rescue compared to the wild-type protein, offering potential as a therapeutic for toxic RNA diseases
  • Can be implemented at lower doses than wild-type proteins
  • Can be modified, increasing stability of synthetic protein for improved efficacy


Repeat expansion diseases are a set of genetic disorders caused by mutations where polynucleotide repeats in certain genes expand beyond the normal threshold, depleting the body’s supply of MBNL proteins. These proteins are critical for regulating alternative exon levels (alternative splicing) during development and across a variety of tissue types. (An exon is any part of a gene that will encode a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing.) Depletion of the MBNL proteins via sequestration by the toxic RNA leads to mis-splicing events responsible for many patient symptoms. University of Florida researchers have created a synthetic MBNL that can displace endogenous MBNL from the toxic RNAs or replace it within the cell. The synthetic proteins provide improved splicing activity compared to the wild-type MBNL protein, and may serve as a powerful therapeutic for repeat expansion diseases.