Project description
Molecular scaffold for in vivo gene therapy applications
Most in vivo gene therapy applications make use of viral vectors that can efficiently deliver the gene(s) of interest inside target cells, mimicking the viral infection process. However, viral-mediated gene delivery suffers from safety issues, such as insertional mutagenesis, and necessitates alternative non viral approaches for delivering genes inside cells. The EU-funded ENDOSCAPE project proposes to employ molecules that facilitate escape from endosomes, the cell organelles responsible for trapping internalised molecules and leading them to degradation. The idea is to generate a molecular scaffold that encompasses these enhancers alongside the gene of interest and a targeting ligand, solving the problem of cytosolic and nucleic delivery of gene therapeutics.
Objective
Gene therapy is one of the most promising treatment options for future advanced therapies in a broad range of diseases. Successful gene delivery requires the recognition of target cells as well as cytosolic and nucleosolic uptake of the gene. Currently, non-viral based gene delivery such as transfection reagents are only suitable for in vitro applications, and clinical gene therapeutics delivery is accomplished via viral vectors, which still has major safety concerns as well as complex and costly manufacturing procedures, preventing future implementation for the treatment of diseases with large patients groups.
In the last 15 years, a class of secondary plant metabolites has been discovered that selectively mediates endosomal escape and cytoplasmic delivery of macromolecules specifically at low endosomal pH, thereby inducing a 40-fold enhanced gene delivery efficacy in vivo. However, endosomal escape enhancers and gene therapeutic product must be applied as two components, thus complicating therapeutic approval and clinical applicability.
The ENDOSCAPE technology platform will develop and collect proof of concept for a non-viral gene delivery technology where endosomal escape enhancers, gene therapeutic product and targeting ligand are all bound to one molecular scaffold. Proof of concept of the ENDOSCAPE technology has a major impact on the therapeutic opportunities for current and future macromolecule drugs for a broad range of diseases and large patient groups.
All this induces new biotech-based businesses, new research projects and creates new technology platforms for development of new macromolecule therapeutics for a broad range of disease indications. The non-viral based ENDOSCAPE technology will enhance therapeutic efficacy with lower therapeutic dose thereby reducing costs of healthcare, improving the health of patients worldwide, and strengthening the competitive landscape of the EU in the worldwide quest for such an advanced technology.
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Programme(s)
Funding Scheme
RIA - Research and Innovation actionCoordinator
10117 Berlin
Germany