Circio and Full Circles Therapeutics are combining circular RNA and single-stranded DNA technologies in research aimed at developing non-viral, re-dosable in vivo cell therapies.

The companies will evaluate Circio’s circVec expression technology with Full Circles Therapeutics’ C4DNA platform, a minicircular single-stranded DNA vector designed to reduce immune recognition.

The collaboration will focus on whether the two technologies can improve the durability of gene expression while allowing therapies to be administered more than once.

Combining circular RNA and single-stranded DNA

Current CAR-T cell therapies are manufactured outside the body before being administered to patients, creating complex production requirements. In vivo approaches aim to generate engineered cells directly inside the patient.

Circio and Full Circles Therapeutics said their combined approach is intended to address some of the limitations of existing in vivo cell therapy technologies, which commonly use mRNA or viral vectors.

Under the research collaboration, Full Circles Therapeutics will design and manufacture C4DNA vectors containing circVec inserts. Circio will then assess the resulting vectors for delivery and expression, as well as immunogenicity, in vitro and in vivo.

Circio CSO Victor Levitsky said: “Circio’s circVec platform has shown specific and durable expression in the spleen in vivo, far outlasting synthetic RNA-based approaches. This shows the significant potential of circVec for in vivo engineering of T-cells and B-cells.”

He added that the collaboration aims to develop a non-viral delivery system that could be re-dosed and manufactured more simply than some existing approaches.

Research will test delivery and expression

Full Circles Therapeutics’ C4DNA technology uses circular single-stranded DNA rather than conventional double-stranded DNA. The company said the format is designed to reduce immune recognition, which could potentially support repeat administration.

The partners will now test whether C4DNA can deliver circVec constructs while retaining the circular RNA technology’s expression characteristics.

Full Circles Therapeutics co-founder and CSO Howard Wu said: “Our C4DNA platform is designed to enable immune-evasive DNA modality with the capacity to deliver extra-larger genetic payloads, while Circio’s circVec technology has demonstrated the potential for increased and durable expression.”

Wu added that the companies aim to develop a non-viral platform for in vivo cell engineering that could combine durable expression and re-dosability with the manufacturing advantages of DNA-based delivery.

Platform remains at research stage

The collaboration is preclinical, with the companies yet to establish whether the combined technology can produce the intended effects in an animal or clinical setting.

Circio has been testing circVec across several potential applications as it seeks to establish where the technology could have therapeutic value. Its recent research collaborations have included work in in vivo cell therapy and gene therapy.

The latest collaboration therefore represents another test of circVec rather than the announcement of a clinical programme or a specific treatment candidate.

The companies have not disclosed financial terms for the collaboration.