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Scientists Develop Safer Method for Gene-Editing Therapy Delivery

Researchers have found a new method of delivering gene-editing medicines to persons with blood illnesses such as thalassaemia and sickle cell disease (SCD), which if used in the clinic might enhance treatment safety and cut costs.

Instead than requiring a round of chemotherapy before delivering externally-edited cells back into the body, the new procedure allows cells to be transformed directly in the body without the need for chemotherapy or radiation treatment.

The technique, co-developed by researchers at the Children’s Hospital of Philadelphia (CHOP) and the University of Pennsylvania’s Perelman School of Medicine, was able to fix mutations in cells from SCD patients, resulting in a more than 90% increase of haemoglobin, the defective protein.

“These findings may potentially transform gene therapy, not only by allowing cell-type specific gene modification in the patient’s body with minimal risk, but also by providing a platform that, if properly tuned, can correct many different disorders,” Laura Breda, PhD, research assistant professor at CHOP and the study’s first author, said in a press release.

The approach was described in the study “In vivo hematopoietic stem cell modification by mRNA delivery,” which was recently published in Science.

“Right now, if you want to treat hematologic diseases like sickle cell disease and beta thalassemia with gene therapy, patients must receive conditioning treatments like chemotherapy to make space for the new, corrected blood cells, which is both expensive and comes with risks,” said Stefano Rivella, PhD, a senior author and professor of pediatrics at CHOP.

According to Rivella, the scientists devised a “one-and-done” strategy for directly altering cells in the body without the need for chemotherapy.

Messenger RNA (mRNA)-based gene-editing tools have been packed into small fatty vesicles known as lipid nanoparticles, which are extremely successful in delivering mRNA into cells (mRNA is an intermediate molecule that acts as a template for protein creation from DNA).

The nanoparticle method is comparable to that utilised in several mRNA-based COVID-19 vaccines, but those vaccines did not target specific cells or organs.

The novel editing approach enabled virtually total repair of cells taken from SCD patients, leading in up to a 91.7% increase in functional haemoglobin and a near complete absence of the sickled blood cells that produce SCD symptoms.

Furthermore, nanoparticles encapsulated with the mRNA for PUMA, a protein that induces cell death, were able to deplete HSCs while allowing the absorption of new bone marrow cells without the need of chemotherapy.

“This is a big step forward in how we think about treating genetic diseases and could expand the access of gene therapies to patients who need them most,” Rivella said.

Source: Penn Medicine News Press Release

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