Sail’s eRNA may result in long-lasting CFTR production

Tech may be option for CF patients who have high unmet medical needs

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Sail Biomedicines’ experimental programmable RNA technology, called Endless RNA or eRNA, appears to result in long-lasting production of the protein that is missing or faulty in people with cystic fibrosis (CF), according to research funded by the CF Foundation.

Producing the protein over an extended period of time may reduce the clinical burden and cost of repeat dosing, according to the company. And because it is programmable, eRNA may be delivered to specific cells, reducing the chance of unwanted side effects.

“We are extremely hopeful about the impact this work could have for the CF community,” Guillaume Pfefer, PhD, CEO of Sail, said in a press release. Sail is part of Pioneering Medicines, an initiative of Flagship Pioneering to develop a portfolio of life-changing treatments.

“The collaboration between Pioneering Medicines and the Cystic Fibrosis Foundation aims to accelerate the path to potential treatments and cures for all people living with cystic fibrosis,” said Paul Biondi, president of Pioneering Medicines and executive partner of Flagship Pioneering.

Pfefer, who is also CEO-partner of Flagship Pioneering, views “eRNA as a potential treatment option for people living with CF, particularly for the 10%-15% of people for whom existing modulator treatments are not an option.”

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CF is caused by mutations in CFTR, a gene that codes for a protein of the same name. The mutations lead to no or impaired production of the CFTR protein, resulting in the disease’s symptoms.

Unlike CFTR modulators, which work by improving the function of the faulty protein, gene therapy aims to allow cells to produce a working version of CFTR. This is expected to work for all patients, regardless of what specific CF-causing mutations they carry.

When producing a protein, cells do not use the DNA directly. Instead, they copy the genetic instructions into a molecule called messenger RNA or mRNA, that serves as a blueprint for the protein. Some experimental treatments use mRNA to make up for the faulty CFTR.

eRNA is encoded with working version of the CFTR protein

Now, Sail has designed an eRNA encoding a working version of the entire CFTR protein, with the goal to provide a treatment option for people with CF who have high unmet medical needs (for example, those who do not tolerate or respond to CFTR modulators).

Made up of stable circular molecules, eRNA is carried aboard proprietary nanoparticles (tiny containers) for delivery into the cells where CFTR is most needed. The company also uses artificial intelligence to help generate eRNA for a range of clinical indications.

Preclinical research showed that eRNA may result in better and longer-lasting production of a fully working version of CFTR in the body compared with mRNA technology, even after a single administration.

“We are excited for Sail to continue to be part of this effort and are encouraged by the progress and potential we are already seeing with eRNA technology,” Biondi said.