Examen
Page URL: https://www.bionews.org.uk/page_138730

Genome editing works in mitochondrial DNA for first time

1 October 2018
Appeared in BioNews 969

Two research groups have, for the first time, used genome editing to successfully treat mitochondrial disease in animals.

As well as possible future treatments for humans, the hope is this approach may one day provide an alternative for mitochondrial replacement therapy used in IVF to produce babies free of mitochondrial disease.

Published last week in Nature Medicine, two back-to-back papers describe how genome editing technologies were harnessed in live mice to help correct a mitochondrial disorder.

'These are remarkable findings that make it possible to even consider doing this in humans,' Dr Martin Picard at the Columbia University Irving Medical Centre in New York City, who was not involved in the work, told Science.

There have been long-standing hopes of using gene therapy to treat diseases of these key organelles – often called the 'powerhouses' of the cell as mitochondria are responsible for energy production, and so when they do not work fully there can be serious health consequences.

Most of the genes that control mitochondrial behaviour are in the mitochondria themselves, separate from the DNA in the nucleus of a cell. This difference makes mitochondrial disease gene therapy very challenging, as tools developed for regular genes will not always translate. There are, however, usually many mitochondria per cell with slightly different DNA, which presents an opportunity.

'One idea for treating these devastating diseases is to reduce the amount of mutated mitochondrial DNA by selectively destroying the mutated DNA, and allowing healthy DNA to take its place,' said Dr Michal Minczuk of the UK's Medical Research Council Mitochondrial Biology Unit in Cambridge, and a senior author of one of the studies.

Both groups made use of the same mouse model of mitochondrial disease, which has the same mutation found in some human patients. Each group then used a different technique to target that specific mutation for elimination.

These techniques – called transcription activator-like effector nucleases (TALENs) and zinc-finger nucleases (ZFNs) – use specific protein sequences to target and chop up target DNA. TALENs and ZFNs were designed to eliminate the mutant mitochondrial DNA in the mice.

The teams used these approaches to genome editing, rather than the more ubiquitous CRISPR/Cas9, because CRISPR uses RNA guide molecules to target the DNA site for cutting. It is more difficult to get RNA into mitochondria than TALEN and ZFN guide proteins, although the latter are more laborious and costly to produce.

The teams inserted the DNA encoding the genome editing tools into a modified virus and infected the mice. One group injected it directly into a leg muscle, while the other group injected it into the mice's circulation, from which it could make it to the muscle cells of the heart. Both studies showed that the gene therapy made it into the muscle cells and successfully targeted the mutant mitochondria, tipping the balance so that healthy mitochondria could take over.

The study that performed vein injection further showed that the metabolism of the cardiac muscle cells seemed to improve following this treatment, indicating the process seemed to have the desired effect.

This is a huge advance for the field, as successful mitochondria editing had previously been achieved only in eggs and embryos, or other cells in the lab.

'The approach appears safe in mice, and we would like to move it into humans,' said Dr Carlos Moraes at the University of Miami Miller School of Medicine in Florida, senior author on the study harnessing TALENs. 'Of course, the delivery of genes to several tissues is still a challenge.'

SOURCES & REFERENCES
RELATED ARTICLES FROM THE BIONEWS ARCHIVE
3 December 2018 - by Jennifer Willows 
A new paper documents three unrelated families where paternal mitochondrial DNA is present in offspring...
29 October 2018 - by Hannah Tippett Simpson 
'Every time somebody decides to have a baby, they're engaging in a game of Russian roulette,' argues  Professor Mary Herbert, a reproductive biologist at the University of Newcastle. Around 60-70 percent of fertilised eggs will never make it to pregnancy. You could see simply being here as a sign that we have beaten the odds...
8 October 2018 - by Dr Rachel Huddart 
Clusters of embryonic stem cells, known as gastruloids, have been found to form structures similar to a developing embryo...
2 July 2018 - by Sarah Pritchard 
Australia may become the second nation to legalise mitochondrial donation, after its Senate endorsed the so-called 'three-person IVF' technique in a recent report...
5 February 2018 - by Sam Sherratt 
The Human Fertilisation and Embryology Authority (HFEA) has granted permission for doctors to create the UK's first 'three-person' children by mitochondrial donation.
29 August 2017 - by Dr César Palacios-González 
Almost a year after the first live birth of a baby following a mitochondrial replacement technique procedure, the US Food and Drug Administration has sent a very strongly-worded letter to the scientist and team responsible for the event...
10 October 2016 - by Giulia Cavaliere 
The announcement of the first baby born using mitochondrial spindle transfer, one of the two techniques that allow the replacement of faulty mitochondrial DNA, caught the UK scientific and bioethics community by surprise...
HAVE YOUR SAY
Log in to add a Comment.

By posting a comment you agree to abide by the BioNews terms and conditions


Syndicate this story - click here to enquire about using this story.