A new study, published in Cell, explores the CRISPR/Cas9 technique to target epigenetics in mice.
Dr Helen Claire O’Neill, Programme Director, Reproductive Science and Women’s Health, University College London, said:
“Genome editing has seen a rapid evolution from the ability to alter genetic sequences, to altering the state or potential of a gene (epigenetic modification), without the need for cutting DNA, or indeed for permanent modification.
“Altering the damaged genetic state in an adult (somatic therapy) to restore function and cure or improve the effect of the disease is the ultimate goal for the many diseases in which there is no current cure. This impressive work applied improved CRISPR technology for the treatment of a range of disorders without the need for permanent genetic editing.
“The “target gene activation” was first tested on a neuromuscular disorder, where they were able to increase muscle mass by restoring silent genes, which compensated for the genetic defect in mice.
“The work also showed the potential ability to change cell fates in order to restore lost functions in organs. To demonstrate this, they altered liver cells to treat diabetes in a mouse model.
“This paper clearly shows the potential therapeutic viability of this technology in human disease models.”
Dr Alena Pance, Senior staff scientist at the Wellcome Trust Sanger Institute, said:
“Overall, the work shows potential for the use of the CRISPR/Cas9 technology, rather than correct genetic defects, to alter gene expression, inducing proteins with crucial roles in certain diseases to improve the symptoms.
“Several different genes were induced in various mouse models of human diseases showing it is a general effect and therefore opening a wide potential application of the system.
“Most of the data is performed in mice expressing Cas9, which leads to general expression of the target gene throughout the body and these effects are not examined further. This potential drawback is mitigated by the demonstration that delivery of Cas9 dead or live together with the targeting system is also able to induce target gene expression and improvement of the symptoms of a particular disease.
“These results bring hope for a targeted gene therapy and widens the application of the technology, but it is a proof of principle where follow up of longer term effects and systematic evaluation of protein expression in various organs and the consequences of these changes are not examined. These issues would need to be investigated in depth before any application in humans is considered.”
*‘In Vivo Target Gene Activation via CRISPR/Cas9-Mediated Trans-Epigenetic Modulation’ by Liao et al. published in Cell on Thursday 7th December.
Dr Alena Pance: “I don’t have any conflicts of interests concerning this work.”
None others received.