MHH researchers write Lancet review on the successes of precision gene therapy.
Symbolically: Professor Büning and Professor Schambach with a "gene taxi" and "gene scissors". Copyright: Isabell Winarsch for Volkswagenstiftung.
"A new era has begun for medicine." Professor Dr Hildegard Büning and Professor Dr Axel Schambach agree on this. The gene therapy experts from the Institute of Experimental Haematology at Hannover Medical School (MHH), together with five other experts, have summarised the current state of gene therapy in a review article for the medical profession that has just been published in the renowned journal "The Lancet". "We can now carry out extremely precise, microsurgical interventions on the genome," explains Professor Schambach. This is made possible by the method of genome editing, also known as genome surgery.
Microsurgery of the genome
Traditional gene therapy attempts to replace the function of a defective gene, for example by introducing a correct version of the gene into the cell. "With genome editing, on the other hand, we can use a kind of scalpel to directly detect individual defective sequences, cut them out and replace them with intact ones," emphasises Professor Büning. "This is tantamount to microsurgery of the genome and literally enables gene repair," adds Professor Schambach. "The same technique can also be used to improve the activity of cell therapeutics, such as those used in oncology, or to specifically switch off genes in order to protect us from attack by certain viruses or to make transplants invisible to the recipient's immune system," says Professor Büning. “We really are on the threshold of a new era: thanks to the targeted correction within the genome that is now possible, we will have an expanded arsenal of therapeutic agents at our disposal."
First gene therapy based on the CRISPR method approved
One tool that has drastically accelerated progress is the CRISPR gene scissors, for which former MHH professor Emmanuelle Charpentier was honoured with the Nobel Prize in Medicine in 2020. "On 16 November, less than a fortnight ago, the world's first gene therapy based on this genetic technology was approved in the UK," reports Professor Büning. People suffering from the blood disorders sickle cell anaemia and beta thalassaemia can now be treated with it. The authors were able to include this milestone in their review article at the very last minute.
For the two MHH professors, this example shows what "fine-tuning in the genes" is already capable of today. "And it will be able to do even more: One idea is to use genetic scissors or 'erasers' in the genome to detect and correct possible malfunctions in common diseases such as high cholesterol levels," says Professor Schambach.
Number of newly authorised gene therapies will increase dramatically
The authors analysed 225 scientific publications for their article. "Gene therapies are increasingly reaching patients, as the many clinical studies that we have analysed show," explains Professor Büning. But this is just the beginning: from 2025, 15 to 20 new gene therapies are expected to be approved in the USA every year. It is particularly important to the authors that the approved gene therapies are then also accessible to patients. "Unfortunately, this has not yet been ensured," emphasises Professor Schambach.
Success is based on interdisciplinary teams
In their article, the researchers emphasise that gene therapy is an extremely complex drug. "The success of gene therapies is based on interdisciplinary collaboration between doctors, researchers, ethicists, regulatory authorities and patient organisations," Professor Schambach is certain. It is also always necessary to critically assess the benefits and risks for those affected and to work on monitoring strategies in order to arrive at better predictions regarding possible side effects.
The MHH authors conclude their article with an outlook. "The methods used in gene therapy will have an enormous impact on the medicine of tomorrow," the two are certain, "because we can also develop new diagnostics using the same strategy we use to search for genetic defects."
You can find the original paper here.
Text: Kirsten Pötzke