BOOST

Bridging oligonucleotide-based therapeutic upregulation of translation (BOOST)

Code: GC-0005

Content:

More than 6000 rare diseases with a defined genetic origin are known, affecting approximately 6% of the global population. Despite advances, effective therapeutic options remain limited due to the rarity, complexity, and high cost of advanced treatments such as gene replacement therapies. Haploinsufficiency - a condition where a single functional gene copy fails to produce sufficient protein for normal physiological functions - is a common underlying cause of many rare diseases. This impacts over 3,000 genes involved in the processes like transcription regulation, development, and cell cycle control, with consequences ranging from intellectual disabilities to developmental anomalies and cancer.

Emerging technologies in genetic testing and nucleotide-based therapies have revolutionized the development of therapies for rare diseases. Nucleotide-based therapies relying on synthetic oligonucleotides are primarily effective for gene silencing and splicing modulation, leaving a significant unmet need for technologies capable of targeted gene upregulation, particularly in haploinsufficient disorders.

The BOOST (Bridging Optimized Oligonucleotides for Stimulated Translation) technology addresses this critical gap. BOOST leverages engineered oligonucleotides to enhance protein translation by associating the highly translated donor mRNAs with the target mRNAs, facilitating ribosomal recruitment and boosting translation efficiency. Its small size facilitates the introduction of chemical modifications for increased stability, and efficient delivery - overcoming common challenges faced by larger RNA-based therapies.

BOOST offers a versatile and scalable platform for addressing haploinsufficiency and other conditions requiring precise protein upregulation. Its modular design enables fine-tuned control, mitigating risks such as immunogenicity, overexpression, and vector size limitations of gene replacement therapies. Furthermore, BOOST’s reliance on endogenous transcriptional regulation preserves the endogenous transcriptional regulation of each target gene, enhancing its safety profile. Compatibility with diverse delivery modalities, including gymnosis, lipid nanoparticles (LNPs), and bioconjugates, broadens its therapeutic applications.

BOOST platform represents a groundbreaking step toward precise, personalized and scalable biomedical technology. BOOST is positioned to redefine therapeutic approaches for rare and genetic disorders.

Consortium partners:
NATIONAL INSTITUTE OF CHEMISTRY
UNIVERSITY OF LJUBLJANA, Faculty of Computer and Information Science
INSTITUT JOŽEF STEFAN
UNIVERSITY OF MARIBOR, Faculty of Medicine and Faculty of Chemistry and Chemical Engineering
Associate partner:
Foundation CTNNB1

Funding:
The project is financed by SRA (ARIS) with a total amount of 21.6 FTE in 3 years of project implementation.
The project will be implemented from 1. 7. 2025 till 30. 6. 2028.

Project phases and their implementation:

WP1 Optimizing the BOOST oligonucleotides to enhance efficiency and minimize off-target effects in genes implicated in haploinsufficient rare disorders, immune-related proteins and differentiation.

WP2 Investigation of chemical modifications to improve stability and cellular uptake.

WP3 Comprehensive transcriptomic and proteomic analyses will assess the effects of BOOST oligonucleotides on cellular processes and identify potential off-target effects.

WP4 Investigation of the molecular mechanisms by which BOOST oligonucleotides facilitate translation.

WP5 Predictive models will be developed to streamline the design of BOOST oligonucleotides using machine learning and bioinformatics tools.

WP6 Various delivery strategies will be explored, including gymnosis, LNP-mediated delivery, and peptide-based systems.

WP7 The efficacy of BOOST oligonucleotides will be tested in animal models. Mouse models of CTNNB1 syndrome and muscular dystrophy will be used to validate therapeutic effects.

WP8 This package ensures effective coordination of project activities, quality assurance, and dissemination of results. It includes stakeholder engagement, outreach to patient organizations, and adherence to open science principles.

Bibliography references arising directly from the implementation of the project:

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Funded by: