Patent Title: Use of miRNAs for the Diagnosis, Prophylaxis, Treatment and Follow-Up of Diseases Involving Macroautophagy Abnormalities
IP Status: Granted European patent; protection coverage reported for the United Kingdom, Germany, France and Türkiye
Technology Area: RNA Therapeutics / Autophagy Modulation / Molecular Diagnostics / Biotechnology
TRL: TRL 4
This technology uses members of the hsa-miR-376 family, particularly miR-376b and their inhibitors, to regulate cellular autophagy for the development of RNA-based therapeutic, diagnostic and disease-monitoring approaches. By targeting key proteins within the autophagy pathway, the platform provides a molecular strategy for conditions in which abnormal autophagic activity contributes to disease.
Technology Overview
The technology is based on controlling macroautophagy, the cellular pathway responsible for degrading and recycling damaged proteins and organelles, through microRNA-mediated regulation. The core approach uses microRNAs from the hsa-miR-376 family or inhibitors directed against these microRNAs to modulate autophagic activity. In the principal implementation, miR-376b directly regulates two important components of the autophagy pathway, BECN1 and ATG4C.
miR-376b targets specific binding sequences within the 3' untranslated regions of BECN1 and ATG4C mRNAs, reducing their intracellular mRNA and protein levels and attenuating autophagic activity. Conversely, inhibition of endogenous miR-376b using molecules such as antagomirs increases BECN1 and ATG4C levels, providing a route to modulate the pathway in the opposite direction. This creates different intervention strategies around the same molecular regulatory axis.
This bidirectional modulation provides a platform for exploring different therapeutic strategies depending on the role of autophagy in a particular disease. The patent scope encompasses the use of the miRNAs or their inhibitors for prophylaxis and treatment as well as for diagnosis and follow-up of diseases associated with abnormal autophagic activity.
The technology is compatible with different nucleic-acid-delivery strategies. Delivery approaches described in the patent include liposomes, polymer-based nanoparticles, cholesterol conjugates, cyclodextrin complexes, polyethyleneimine polymers and protein complexes. This provides flexibility for pharmaceutical development of formulations intended to deliver the selected miRNA or inhibitor to target tissues.
Development is currently at laboratory and preclinical stage. The molecular mechanism for regulating autophagy has been demonstrated in cellular systems, animal studies have been completed, and toxicity studies have been conducted. Progression towards clinical development requires certified toxicity studies and the relevant ethical and regulatory approvals before clinical trials can begin.
Problem / Market Need
Autophagy is a fundamental cellular mechanism responsible for maintaining homeostasis through the removal and recycling of damaged proteins and organelles. Excessive or insufficient autophagic activity is associated with diverse pathological processes, including cancer, neurodegenerative disorders and a range of metabolic, inflammatory and other diseases.
Rather than broadly activating or inhibiting the entire autophagy pathway, targeting molecular regulators that control specific parts of this process creates opportunities for more directed therapeutic and diagnostic strategies. MicroRNAs represent such regulatory nodes because they can control the expression of biologically important target genes.
The miR-376 platform provides a molecular approach for regulating defined autophagy-related targets and creates a basis for developing RNA therapeutics, diagnostic strategies and treatment-monitoring tools that can be adapted to the biological context of different autophagy-associated diseases.
Key Advantages
- Direct regulation of the key autophagy proteins BECN1 and ATG4C through miR-376b
- Potential to modulate autophagy in different directions using miRNAs or corresponding inhibitors
- Simultaneous control of two important components acting at different stages of the autophagy pathway
- Platform potential for therapeutic use as well as diagnosis and treatment follow-up
- Compatibility with multiple nucleic-acid and drug-delivery approaches
- Adaptable platform for different disease areas associated with abnormal autophagy
- Molecular mechanism supported by laboratory and preclinical development work
- Potential for development as an accessible and scalable RNA-based platform
Applications
- Development of autophagy-modulating RNA therapeutics
- miRNA-inhibitor and antagomir-based therapeutic approaches
- Molecular diagnosis and monitoring of diseases associated with abnormal autophagy
- Oncology research and therapeutic development, including breast and liver cancer
- Research and therapeutic development for neurodegenerative diseases
- Autophagy-targeted research in liver and cardiovascular diseases
- Autophagy modulation in inflammatory, autoimmune and infectious diseases
- RNA-based research for metabolic and cellular-stress-related disorders
Relevant Industries
- Biotechnology
- Pharmaceuticals and Biopharmaceuticals
- RNA Therapeutics
- Molecular Diagnostics
- Oncology
- Neurodegenerative Disease Technologies
- Precision Medicine and Biomarkers
- Drug Delivery Systems
Technology Readiness Level & Validation
Technology Readiness Level: TRL 4
The technology has been validated at laboratory scale, with studies addressing the active molecular mechanism and biological effects at cellular level. Regulation of autophagic activity through miR-376b-mediated modulation of BECN1 and ATG4C has been demonstrated in cell models.
Animal experiments have been completed, and toxicity studies have been conducted. Results of the producable drug formulation or product-level prototypes are under the development phase. product/prototype development remains ongoing.
Certified toxicity studies and the required ethical and regulatory approvals will be necessary before progression to clinical development. Subsequent development is expected to require Phase I and Phase II clinical studies.
The technology was developed through research supported under the TÜBİTAK 1001 Programme.
Intellectual Property
European Patent: EP2622075B1
European Patent Publication: EP2622075A1
International Patent Publication: WO2012044265A1
International Application: PCT/TR2010/000192
Patent Title: Use of miRNAs for the Diagnosis, Prophylaxis, Treatment and Follow-Up of Diseases Involving Macroautophagy Abnormalities
Priority / Filing Date: 27 September 2010
European Publication Date: 7 August 2013
European Patent Grant Date: 2 March 2016
Applicant / Assignee: Sabancı University
Protection Coverage Reported in the Technology Form: United Kingdom, Germany, France, Türkiye
Commercialisation Status
The technology is currently in product/prototype development and is available for licensing. Further development requires translation of the laboratory- and preclinical-stage biological mechanism into a candidate product and delivery formulation suitable for regulated drug development and subsequent clinical evaluation.
Collaboration Opportunities
- Licensing
- Scientific consultancy
- Joint R&D and co-development
- Preclinical and clinical development / validation
- Manufacturing and product-development collaboration
- Investment and commercial partnership
- Development programmes aimed at advancing TRL
Potential partners may include biotechnology companies developing RNA therapeutics and oligonucleotide drugs, pharmaceutical companies active in oncology and neurodegenerative diseases, nucleic-acid-delivery technology developers, CROs specialising in preclinical and clinical development, and molecular-diagnostics companies.
Priority areas for joint development include formulation of the miRNAs or their inhibitors using suitable delivery systems, completion of certified toxicity studies, disease-specific preclinical validation, selection of clinical candidates, and development of regulatory-compliant Phase I–II programmes.
Inventors
Inventors: Devrim Gözüaçık, Gözde Korkmaz
Contact
For licensing, preclinical or clinical development, joint R&D or other collaboration opportunities related to this technology, please contact Sabancı University Technology Transfer Office (SUATT) at dpe.suatt@sabanciuniv.edu.