Tiny livers grown from skin cells in a Tshwane laboratory are at the centre of South African scientists’ efforts to prevent adverse drug reactions in Africa.
Their work, much of it conducted with a tiny pair of “molecular scissors”, aims to identify which Western medicines are toxic to Africans.
After decades of scientific advances, the Council for Scientific and Industrial Research (CSIR) reckons it is only two years away from finalising technology that matches drugs with patients based on their genetic makeup.
The “scissors” allow scientists to edit genomes by altering DNA sequences and modifying gene function.“We aim to create cellular models which include African mutations by using molecular scissors,” said Dr Janine Scholefield, a senior researcher at the CSIR.“
The engineering process is such that we can create a specific break in the DNA, and then give the cell we are targeting another DNA template. The cell will then repair the DNA as per that template.
“It means, barring some size restrictions, we can make any change in the genome.”
A major breakthrough with the molecular scissors, known in their most recent incarnation as CRISPR-Cas 9, is that they can “target any sequence in the genome” — something traditional gene therapy was struggling to do.
“Molecular scissors essentially contain ‘GPS’ co-ordinates of where to make the correction,” said Scholefield.
The second technique involves using skin to create stem cells. “At our laboratory we can combine the genome engineering technology with what is called induced pluripotent stem cells,” said Scholefield.
“Using this tech, we can take a tiny piece of skin and turn it into a stem cell, which can become any cell in the body. One of the things you can turn it into is a liver cell.”
This is of “major importance to our region” because many drugs from the West have not been tested on people of African descent, and can cause toxicity in the liver.
“Drugs trials take place on a very narrow genetic group, and often it is mainly Europeans. The drugs then get rolled out in Sub-Saharan Africa — but this is the most genetically diverse region in the world, and many people’s liver genes here are not the same as Europeans’,” said Scholefield.
“We cannot redo the entire clinical trial, but what if we could create liver cells in a dish so we can test for specific drug responses using cells that have African genetics?”
That is exactly what they’re doing. “We are using different drugs on the liver cells we are making to see which cause toxicity and which don’t.
“This means down the line a doctor could test a patient to see what drugs will or won’t work for them, and how to avoid the ones that will make them sick.
“Other people in the world are doing similar projects, but we believe that our method will be most cost-effective.”
Ultimately, the CSIR wants to provide a digital platform clinicians can use to see which drugs will agree with which patients.
Their research complements work on gene therapy taking place at Wits University (with a focus on hepatitis B) and the University of Pretoria (with a focus on HIV).
Professor Abdullah Ely, from the antiviral gene therapy research unit at Wits, told the Sunday Times: “We develop gene therapeutics against viruses. The virus that is the focus of research is the hepatitis B virus, which infects the liver and causes both acute and chronic hepatitis B.”
The latter can lead to liver damage as well as cancer of the liver.
“The uses of gene therapy are many and its potential is still enormous. Currently there is no licensed cure for chronic hepatitis B but with gene therapy, specifically using gene-editing technologies, it is possible to eliminate the virus or permanently disable it,” he said.
Professor Michael Pepper, director of the Institute for Cellular and Molecular Medicine at the University of Pretoria, said the therapeutic use of CRISPR should not be confused with “genome editing involving gametes [egg and sperm]”.
In November last year, a Chinese doctor sparked worldwide alarm when it was revealed he had delivered two gene-edited babies. Using CRISPR technology, he had fiddled with their DNA to remove any chance of them getting HIV, but he may also have considerably shortened their lifespans.
Would you like to comment on this article?
Sign up (it's quick and free) or sign in now.
Please read our Comment Policy before commenting.