Scientists have repurposed CRISPR to target the repetitive RNA sequences responsible for several genetic diseases.
They suggest the approach could one day be used to treat diseases including Huntington's disease, hereditary amyotrophic lateral sclerosis (ALS) and myotonic dystrophy.
'We are really excited about this work because we not only defined a new potential therapeutic mechanism for CRISPR/Cas9, we demonstrated how it could be used to treat an entire class of conditions for which there are no successful treatment options,' said co-first author Dr David Nelles of the University of California, San Diego (UCSD).
Within cells, DNA is transcribed into RNA to produce proteins. Certain diseases are caused by mutations known as microsatellite repeat expansions – repetitive DNA sequences, which when transcribed cause a build up of toxic proteins known as RNA foci.
In a previous study published last year, the team adapted CRISPR/Cas9 to track RNA. They have now applied this technique, known as RCas9, to remove microsatellite repeat expansions from RNA.
The scientists showed RCas9 could remove 95 percent or more of RNA foci linked to myotonic dystrophy type 1 and type 2, one type of ALS, and Huntington's disease. It could also remove 95 percent of repeat RNA in cells taken from patients with myotonic dystrophy, and restore normal binding of MBNL1, a protein which binds RNA but is usually unable to do so in myotonic dystrophy type 1.
'There are more than 20 genetic diseases caused by microsatellite expansions in different places in the genome,' said Dr Ranjan Batra of UCSD, and co-first author. 'Our ability to program the RCas9 system to target different repeats, combined with low risk of off-target effects, is its major strength.'
As RNA is short-lived, any changes resulting from RNA-targeted genome editing would not be permanent. Speaking to KPBS, Dr Batra said this could be preferable in case of 'off-target effects'. Additionally, a viral delivery system for RCas9 could be effective for perhaps five to 10 years, according to senior author Professor Gene Yeo of UCSD.
The team also made a smaller version of Cas9 so that RCas9 could be delivered to patient's cells using a viral vector, which can be too small to hold Cas9. Professor Yeo said the next step would be to establish whether these viral vectors would elicit an immune response in vivo.
The study was published in Cell.
Sources and References
-
San Diego Scientists Tweak Gene Editing Tool To Target RNA
-
Researchers Use CRISPR to Destroy Pathogenic RNA Species Linked to Huntington's Disease, ALS
-
New version of DNA editing system corrects underlying defects in RNA-based diseases
-
Elimination of Toxic Microsatellite Repeat Expansion RNA by RNA-Targeting Cas9
-
CRISPR Corrects RNA-based Disease Defects
Related Articles
New advance in DNA base editing tools
Scientists have developed the genome editing technique known as 'base editing' to turn adenine-thymine base pairs back to guanine-cytosine...
RNA editing tools could create new disease therapies
A new molecular tool to change individual letters in an RNA sequence may open up new possibilities for gene therapy...
Huntington's disease in mice partly reversed using CRISPR
Eliminating the faulty protein that causes Huntingdon's disease goes some way to reversing disease progression in mice, a study has found...
MIT CRISPR team turn to RNA
The team that developed the CRISPR/Cas9 DNA-editing technique have now developed a new system that could allow RNA editing...
Accurate editing of human DNA now possible, say scientists
A molecular technique that enables any part of the human genome to be altered with extreme precision has been hailed by scientists as a breakthrough in genetics...
Leave a Reply
You must be logged in to post a comment.