RAMOT at Tel Aviv University Ltd.

Harnessing inhibitory RNA based- nanoparticles for therapeutic intervention in blood cancers

Posted by RAMOT at Tel Aviv University Ltd.Responsive · Innovative Products and Technologies · Israel

Summary of the technology

Modulating T cells functions by down regulating specific genes using RNA interference (RNAi) holds tremendous potential in advancing targeted therapies in many immune related disorders including cancer, inflammation, autoimmunity and viral infections. Hematopoietic cells, in general, and primary T lymphocytes, in particular, are notoriously hard to transfect with small interfering RNAs (siRNAs). Herein, we describe a novel strategy to specifically deliver siRNAs to murine CD4+ T cells using targeted lipid nanoparticles (tLNPs). To increase the efficacy of siRNA delivery, these tLNPs have been formulated with several lipids designed to improve the stability and efficacy of siRNA delivery. The tLNPs were surface functionalized with anti-CD4 monoclonal antibody (mAb) to permit delivery of the siRNAs specifically to CD4+ T lymphocytes. Ex vivo, tLNPs demonstrated specificity by targeting only primary CD4+ T lymphocytes and no other cell types. Systemic intravenous administration of these particles led to efficient binding and uptake into CD4+ T lymphocytes in several anatomical sites including the spleen, inguinal lymph nodes, blood and the bone marrow. Silencing by tLNPs occur in a subset of circulating and resting CD4+ T lymphocytes. Interestingly, we show that tLNPs internalization and not endosome escape is a fundamental event that takes place as early as one hour after systemic administration that determine tLNPs efficacy. Taken together, these results suggest that tLNPs may open new avenues for the manipulation of T cell functionality and may help to establish RNAi as a therapeutic modality in leukocyte-associated diseases.
Project ID : 10-2016-962

The current treatment of multiple myeloma (MM) included standard chemotherapy and small molecules such as the proteasome inhibitor and the immunomodulatory drugs. Although these drugs have improved the response and survival of MM patients, MM is still an incurable disease. Drug resistance and disease refractoriness are the common terminal pathways leading to patients’ mortality. Therefore, the development of novel effective treatments is needed.

Our approach allows the delivery of combination of siRNAs molecules that could silence simultaneously several genes specifically in MM cells and eradicate MM cells in vivo. Currently, no other nanomedicine approaches are available for treatment of B-cell malignancies.
We develop highly selective lipid-based nanoparticles, entrapping specific combination of siRNAs that will induce therapeutic gene silencing and eradicate multiple myeloma cells as a prototypic blood cancer

Today’s leading treatment modality calls for combination of different drugs to effectively control and treat malignancies. This technology as a novel drug may be used as a standalone therapy, or as a combination therapy with other drugs for treating cancer:
• Targeting simultaneously several targets.
• May be used as a standalone therapy.

1. A collection of targeted lipid nanoparticles (LNPs) appropriate for treatment of subclasses of multiple myeloma (MM) patients (personalized medicine for MM patients).
2. Therapeutic targeted lipid nanoparticles for patients with others CD38-positive mature B cell neoplasms such as; Chronic lymphocytic leukaemia (CLL), Mantle cell lymphoma (MCL), Follicular lymphoma (FL) and Hairy cell leukemia (HCL).

Provisional patent application has been filed

Lead Inventor: Prof. Dan Peer

Project manager

Adi Elkeles
BD Manager

Project researchers

Dan Peer
T.A.U Tel Aviv University, Life Sciences
Cell Research and Immunology

Related keywords

  • Micro- and Nanotechnology
  • Medicine, Human Health
  • Biology / Biotechnology
  • Micro- and Nanotechnology related to Biological sciences
  • Micro- and Nanotechnology related to Biological sciences
  • Therapeutic
  • Clinical Medicine
  • Nanotechnology
  • Nano Medicine

About RAMOT at Tel Aviv University Ltd.

Technology Transfer Office from Israel

Ramot is Tel Aviv University's (TAU) technology transfer company and its liaison to industry, bringing promising scientific discoveries made at

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