OLIGOMED - Oligonucleotides for medical applications

OLIGOMED Work Packages

In order to achieve the overarching aims and to successfully deliver a flexible platform technology that can be adapted to different medical problems, OLIGOMED has defined research objectives addressed by four interlocked Research & Development (R&D) work packages (WPs). These are briefly described below.

The R&D WPs consist of:

an overarching WP for systems development
an application WP for regulation of gene expression
an application WP for non-canonical DNA structures
an application WP for self-assembled DNA nanostructures

The WPs comprise design, synthesis, analysis, delivery and therapy.

Targets are cancer, Huntington's Disease and cardiovascular diseases.

Three additional WPs cover logistics in training, dissemination and management.

WP structure of OLIGOMED

Integrated workpackages form the basis of R&D, training, dissemination and management of our network.

Beneficiaries

Work Package 1

Objective:

To construct a technology platform of innovative ON therapeutics encompassing design, synthesis, analysis and delivery of diverse ON based therapeutics.

This overarching WP includes all aspects of ON chemistry and biology; functional ONs are key to the platform’s success; targeted delivery will be a major focus point.

This WP will employ all ESRs, where they will perform the design and method development of building blocks and especially ON constructs for use in WP2-4 and share the knowledge across the consortium. It includes training in making, analysing and using ONs (tools), and in the design of the targets (strategy).

WP1 is led by UGENT and Biovectis.

Work Package 2

Objective:

To regulate the expression of mRNA by either depleting it through antisense strategy that targets specific mRNA’s, or by increasing the translation through RNA activation or targeting of suppressing miRNAs.

In addition, both up and down regulation will be attempted by manipulating the cap-independent IRES function in oncogenes as a new modality. Target diseases are HD, cancer, and cardiovascular diseases.

This WP will employ ESRs 1-6.

WP2 is led by UNIUD and AZ.

Work Package 3

Objective:

To apply the ONs in the formation of non-canonical DNA structures to regulate gene expression and enzyme function.

This WP entails two approaches: triple helix and GQ formation.

The former is part of a therapy discovery program addressing HD and Friedreichs ataxia (FRDA).

Modified GQs with increased stability and defined folding will be used as decoy to target telomerase activity and to manipulate gene-expression in systems where GQs are essential regulatory parts; both are valid targets for cancer treatment.

This WP will employ ESRs 7-10.

WP3 is led by SLL and KI.

Work Package 4

Objective:

To form self-assembled ON nanostructures for targeted cell killing using novel modes of action.

We will use DNA and RNA based self-assembled nanopores (NP) that embed into membranes and lead to cell death, or lead to scaffolds that deliver ONs onto the cell cytoplasm.

Conjugated systems of the NP combined with cell targeting systems, immune stimulants, and chromophores for photodynamic therapy will form a combination therapy in a novel and truly modular system

This WP will employ ESRs 11-15.

WP4 is led by INSERM and SB.

Beneficiary acronyms:

SOTON	University of Southampton	UGENT	Universiteit Gent
CNRS	Centre National de la Recherche Scientifique	AZ	AstraZeneca
KI	Karolinska Instituted	UNIUD	Università degli Studi di Udine
BIOVECTIS	BioVectis	UCAM	University of Cambridge
SLL	Stockholms Läns Landsting	RISE	Research Institutes of Sweden
INSERM	Université de Bordeaux	SB	Sixfold Bioscience