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Gene therapy skin grafts for obesity and diabetes

07 August 2017

By Annabel Slater

Appeared in BioNews 912

A proof-of-concept study in mice has demonstrated how skin grafts could deliver gene therapy for obesity and diabetes.

'We think this platform has the potential to lead to safe and durable gene therapy, in mice and we hope, someday, in humans, using selected and modified cells from skin,' said senior author Dr Xiaoyang Wu of the University of Chicago, Illinois.

The technique explores the potential of glucagon-like peptide 1 (GLP1), a hormone which could help to treat conditions like diabetes and obesity. GLP1 reduces appetite and stimulates the release of insulin to lower blood sugar, but does not last long in the blood and is challenging to deliver orally.

The researchers used CRISPR to edit skin stem cells taken from newborn mice. They inserted a modified version of the GLP1 gene, designed to increase the duration of the hormone, and a genetic 'switch' to turn the gene on in the presence of an antibiotic.

They grew the skin stem cells into a skin organoid, and grafted them onto mice. When the mice were fed small amounts of antibiotic, they successfully produced modified GLP1, which lasted for three months, and showed higher levels of insulin and lower levels of glucose. 

The researchers also tested feeding the mice a high-fat diet. Compared to controls, the mice with modified GLP1 skin grafts put on less weight.

Dr Wu said the skin graft method could be safer than using engineered viral vectors to edit genes in patient's own tissues, as viruses 'may cause a very strong immune reaction and inflammation in vivo.' He added that lab-grown skin grafts have been used clinically for some time to treat burns, and have been proven safe.

Being able to control the gene expression using a drug would also allow doctors to calibrate how much of the enzyme enters a patient’s bloodstream.

'We think this can provide a long-term safe option for the treatment of many diseases,' Dr Wu said. 'It could be used to deliver therapeutic proteins, replacing missing proteins for people with a genetic defect, such as haemophilia. Or it could function as a metabolic sink, removing various toxins.'

Dr Jeffrey Millman of Washington University, St Louis, who was not involved in the study, told The Scientist that more research would be needed to ensure that neither the genome editing nor the stem cell culturing method inadvertently introduce dangerous mutations.

SOURCES & REFERENCES
Genetic Engineering and Biotechnology News | 02 August 2017
 
New Scientist | 03 August 2017
 
Cell Stem Cell | 03 August 2017
 
Science Daily | 03 August 2017
 
The Scientist | 04 August 2017
 

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