In vitro & biodistribution analysis of morphology-controlled polymeric gene delivery nanocarriers (POLYMORPH)

Obiettivo

Gene therapy holds the potential to be an enabling technology to truly cure (rare) diseases by directly correcting errors in the patient’s genetic database underlying the disorder. For these corrections therapeutic nucleic acids (NAs) are typically used. However, the precise and efficient delivery of these NAs remains a critical bottleneck, hindering the full-scale clinical implementation of gene therapy. NAs are large, highly charged and unstable molecules, hampering transport and passing (intra)cellular barriers after administration. To mitigate this, NAs are typically packaged into nanocarriers, where lipid-based systems (LNPs) are the current state-of-the-art. Although an effective strategy to protect NAs, selective tissue targeting remains a tremendous challenge. Nanoparticles (NPs), including LNPs, tend to preferentially accumulate in the liver, limiting treatment of any disorder affecting other tissues and organs.

The ERC PoC POLYMORPH project builds on the promising results of the original ERC Starting Grant project and aims to validate the use of nanoparticle (NP) morphology to redirect nanocarrier accumulation away from the liver. Morphological control of NA-loaded NPs is uniquely facilitated by a novel formulation strategy recently developed in the ERC Starting project. This novel approach has the potential to provide a superior alternative to the current, yet suboptimal, LNPs.

POLYMORPH will achieve this validation through comprehensive in vitro studies and preliminary in vivo experiments, laying the groundwork for future clinical applications. The project is further strengthened by the active involvement of multiple stakeholders, including academic researchers, the pharmaceutical industry, medical centers, regulatory science experts, and a knowledge transfer organization. This broad engagement maximizes the potential for clinical, commercial and societal impact, ensuring a strong pathway towards real-world implementation.