MRNA encoding the human CFTR gene

MRNA encoding the human CFTR gene is an investigational substance developed as a potential treatment for cystic fibrosis. It is also known by the development code ARCT-032.^[1] The substance is designed to deliver genetic instructions directly to cells in the lungs.

What is mRNA encoding the human CFTR gene?

MRNA encoding the human CFTR gene is a messenger RNA (mRNA) therapy. It is not yet an authorised medicine and remains an investigational substance. The active substance carries the genetic code for the human cystic fibrosis transmembrane conductance regulator (CFTR) protein, which is defective or missing in people with cystic fibrosis.^[1] In the trial register, the substance is listed under the name "MRNA encoding the human CFTR gene" and studied as ARCT-032.

How does mRNA encoding the human CFTR gene work?

The substance is designed to deliver mRNA that encodes the human CFTR protein directly into lung cells. Once inside the cells, the mRNA provides the instructions for producing a functional CFTR protein. This approach aims to address the underlying genetic cause of cystic fibrosis by helping cells make the protein that is missing or not working properly in people with the condition.

Which conditions is it used or studied for?

• Cystic fibrosis — a genetic condition that affects the lungs and other organs, causing thick mucus to build up. The only registered trial for this substance studied people with this condition.^[1]

How is mRNA encoding the human CFTR gene given?

The substance is given by inhalation, meaning it is breathed into the lungs as a mist or powder. The trial tested multiple ascending doses, which means participants received increasing amounts of the treatment over the course of the study.^[1]

What do the clinical trials show?

One completed Phase 2 trial has investigated mRNA encoding the human CFTR gene in people with cystic fibrosis. The trial was open-label, meaning both the researchers and the participants knew which treatment was being given.^[1] It enrolled 30 participants.^[1]

What is being measured in the trial?

The trial's main goal was to assess safety and tolerability. The researchers looked at adverse events (side effects), adverse events of special interest, and serious adverse events, recording how often they occurred, how severe they were, and whether they were related to the dose.^[1] They also measured changes in vital signs, physical examination findings, and laboratory test results. A particular focus was checking for bronchospasm — a sudden narrowing of the airways — by measuring changes in forced expiratory volume in one second (FEV1), a standard test of lung function, before and after each dose.^[1]

Who can take part in these trials?

The completed Phase 2 trial enrolled 30 people with cystic fibrosis. The trial is now completed, meaning it is no longer recruiting participants.^[1]

What side effects are known?

The trial measured side effects as its primary outcome, but the registry record does not report the results. No side effect information is available from the sources provided.