CRISPR-GENTechnik: Progressive therapies on the way to the clinic

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Die neuesten Fortschritte in der CRISPR-Genomeditierung versprechen effektive Therapien gegen Blutkrankheiten im Klinikalltag.
The latest progress in CrisPR genomed serves effective therapies against blood diseases in everyday clinical practice. (Symbolbild/natur.wiki)

A new wave of genetic therapies comes to the fore-while the field is fighting at the same time as the challenge, of the first generation of expensive and complex crispr treatments to make people accessible.

"Casgevy showed a clear benefit for general health, as well as for the physical, emotional, social and functional well -being," said Franco Locatelli, a pediatric hematologist and oncologist at Bambino Gesù Kind Hospital in Rome. He added that the therapy "has the potential to offer a unique functional healing".

Although other companies are trying to imitate Casgevy's success, the complexity and the high price of the treatment have aroused concerns that it will not be available to many people.

Stuart Orkin, a pediatric hematologist and oncologist at the Harvard Stamm cell institute in Cambridge, Massachusetts, said at the meeting: "The compelling necessity now consists in developing effective and safe therapies that are easily accessible to the many patients who could benefit from it."

Fetal Hemoglobin as a solution

Both β-thalassemia and sickle cell anemia are caused by mutations in one of the genes that code for hemoglobin, the oxygen-bearing molecule in red blood cells.

long -term advantages

One of the concerns of the advisory committee was the uncertainty about how long the effects of Casgevy will last. At the hematology conference in San Diego, researchers presented data that show that the advantages of both illnesses can last for at least five years. Treatment with Casgevy reduced the need for blood transfusions in patients with β-thalassemia and hospital stays in patients with sickle anemia. Over 90 % of the participants reported that they had no pain crawls at least 12 consecutive months - painful episodes caused by the blockade of blood vessels by malformed blood cells.

This is proof of the principle of genetic therapies that encouraged a large number of other companies and academic researchers in the field of area. During the meeting, Justin Eyquem, a cancer immunologist at the University of California in San Francisco, presented results of animal experiments that used CrisPR-CAS9 arrangements for the development of cancer-fighting immune cells called Car-T cells. Paula Rio, an immunologist at the Autonomous University of Madrid, reported on how to test several genetic therapy techniques to develop therapy against fanconi anemia, a rare genetic disease with increased risk of cancer.

Others remain in the sickle cell anemia. Beam Therapeutics in Cambridge, Massachusetts, presented data from his first clinical study on treatment of sickle cell anemia that uses a technology called Base Editing. This method is related to Crispr, but carries out more precise changes in the DNA strand as Crispr. The values ​​of the fetal hemoglobin rose to more than 60 % of total hemoglobin in seven treated people by the end of October.

life -threatening risks

Such therapies, including Casgevy, bring risks with them: The death of a participant in the beam study was probably the result of chemotherapy that was used to remove unmanipulated blood stem cells from the body, which is necessary to create space for the processed cells. This chemotherapy, which is called Busulfan, can also lead to infertility.

At the meeting, Beam presented at the meeting with another gene therapy, Prime Medicine, the results of animal experiments that tested paths to make this process more secure. Beam used an antibody that specifically attacks blood stem cells to reduce their number, but to leave other cells intact. The company then changed its base editing therapy in such a way that the processed cells were immune to treatment with the antibody. Animal studies indicated that this approach could work: edited cells remained in treated animals for at least six months.

Prime Medicine presented data for a similar approach to avoiding chemotherapy using recent processing technology, which is known as prime editing. Prime Editing can insert or delete DNA with more precision than the Crispr-Cas9 editing and is more versatile than base editing.

Overall, these approaches and others could be crucial to make gene therapies for blood diseases more secure and more accessible, said John Tisdale, hematologist at the National Heart, Lung, and Blood Institute in Bethesda, Maryland. "The way we are currently doing is simply not scalable," he added. "But things move quickly."