Descrizione del progetto
Substrato molecolare per applicazioni di terapia genica in vivo
La maggior parte delle applicazioni di terapia genica in vivo fa uso di vettori virali in grado di fornire in modo efficiente i geni di interesse all’interno delle cellule bersaglio, imitando il processo di infezione virale. Tuttavia, il rilascio di geni attraverso virus non è scevra di problemi di sicurezza, quali ad esempio una mutagenesi inserzionale, e pertanto richiede approcci alternativi non virali per il rilascio di geni all’interno delle cellule. Il progetto ENDOSCAPE, finanziato dall’UE, propone di impiegare molecole che agevolino la fuga dagli endosomi, gli organuli cellulari responsabili dell’intrappolamento delle molecole interiorizzate e della loro degradazione. L’idea è quella di generare un substrato molecolare che comprenda tali potenziatori insieme al gene di interesse e un ligando di destinazione, risolvendo il problema del rilascio citosolico e nucleico della terapia genica.
Obiettivo
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.
Parole chiave
Programma(i)
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Vedi altri progetti per questo bandoBando secondario
H2020-SC1-2018-Single-Stage-RTD
Meccanismo di finanziamento
RIA - Research and Innovation actionCoordinatore
10117 Berlin
Germania