A5102767078- RNA Interference and Gene Delivery
- Chronic Lymphocytic Leukemia Research
- Advanced biosensing and bioanalysis techniques
- Immunodeficiency and Autoimmune Disorders
- Immunotherapy and Immune Responses
- MicroRNA in disease regulation
- Lymphoma Diagnosis and Treatment
- Galectins and Cancer Biology
- Acute Lymphoblastic Leukemia research
- Immune Cell Function and Interaction
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Virus-based gene therapy research
- Chronic Myeloid Leukemia Treatments
- Acute Myeloid Leukemia Research
- Cytokine Signaling Pathways and Interactions
- Bacillus and Francisella bacterial research
- Yersinia bacterium, plague, ectoparasites research
- RNA Research and Splicing
- Macrophage Migration Inhibitory Factor
- Nanoplatforms for cancer theranostics
- Immune cells in cancer
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Multiple Myeloma Research and Treatments
- RNA modifications and cancer
- Nuclear Receptors and Signaling
Tel Aviv University
2016-2025
Center for NanoScience
2022
Centre de Nanosciences et de Nanotechnologies
2016
The University of Texas MD Anderson Cancer Center
2007-2014
Tel Aviv Sourasky Medical Center
2010-2013
The University of Texas at Austin
2010
Ben-Gurion University of the Negev
2000-2008
Soroka Medical Center
2002-2005
GTx (United States)
2005
Lipid nanoparticles (LNPs) are the most advanced nonviral platforms for small interfering RNA (siRNA) delivery that clinically approved. These LNPs, based on ionizable lipids, found in liver and now gaining much attention field of therapeutics. The previous generation lipids varies linker moieties, which greatly influences vivo gene silencing efficiency. Here novel amino moieties such as hydrazine, hydroxylamine, ethanolamine designed synthesized. formulated into LNPs screened their...
Ionizable lipid-based nanoparticles (LNPs) are the most advanced non-viral drug delivery systems for RNA therapeutics and vaccines. However, cell type-specific, extrahepatic mRNA is still a major hurdle, hampering development of novel therapeutic modalities. Herein, ionizable lipid library synthesized by modifying hydrophobic tail chains linkers. Combined with other helper lipids utilizing microfluidic mixing approach, stable LNPs formed. Using Luciferase-mRNA, mCherry mRNA, Cre together...
Messenger RNA (mRNA) lipid nanoparticle (LNP) vaccines have emerged as an effective vaccination strategy. Although currently applied toward viral pathogens, data concerning the platform's effectiveness against bacterial pathogens are limited. Here, we developed mRNA-LNP vaccine a lethal pathogen by optimizing mRNA payload guanine and cytosine content antigen design. We designed nucleoside-modified based on F1 capsule antigen, major protective component of Yersinia pestis, etiological agent...
MicroRNAs (miRNAs) regulate gene expression by post-transcriptional inhibition of target genes. Proangiogenic small extracellular vesicles (sEVs; popularly identified with the name "exosomes") a composite cargo miRNAs are secreted cultured stem cells and present in human biological fluids. Lipid nanoparticles (LNPs) represent an advanced platform for clinically approved delivery RNA therapeutics. In this study, we aimed to (1) identify responsible sEV-induced angiogenesis; (2) develop...
Chemo-immunotherapy is a combination of "standard-of-care" chemotherapy with immunotherapy and it considered the most advanced therapeutic modality for various types cancers. However, many cancer patients still poorly respond to current regimen chemo-immunotherapy suggest nanotherapeutics as boosting agent. Recently, heme oxygenase-1 (HO1) shown act an immunotherapeutic molecule in tumor myeloid cells, addition general chemoresistance function cells suggesting that HO1-targeted therapeutics...
Abstract Multiple myeloma (MM) is a cancer of differentiated plasma cells that occurs in the bone marrow (BM). Despite recent advancements drug development, most patients with MM eventually relapse and disease remains incurable. RNA therapy delivered via lipid nanoparticles (LNPs) has potential to be promising treatment, however, its clinical implementation limited due inefficient delivery non‐hepatic tissues. Here, targeted (t)LNPs designed for payload are presented. The tLNPs consist novel...
Abstract Several cytokines and growth factors that stimulate the proliferation of acute myelogenous leukemia (AML) cells transduce their signals by activating transcription factor Janus-activated kinase 2 (JAK2). Accordingly, inhibition JAK2 or its downstream signaling pathways suppresses AML cells. Because (E)-3(6-bromopyridin-2-yl)-2-cyano-N-((S0-1-phenylethyl)acrylamide) (WP1066) is a novel analogue inhibitor AG490, we tested activity in investigated mechanism action. Using clonogenic...
Survival of chronic lymphocytic leukemia (CLL) cells in vivo is supported by the tissue microenvironment, which includes components extracellular matrix. Interactions between tumor and matrix are part mediated CD44, whose principal ligand hyaluronic acid. Here, we show that CD44 more highly expressed on CLL clinically progressive immunglobulin heavy chain variable gene (IGHV)-unmutated subtype than IGHV-mutated type. Engagement activated phosphatidylinositol 3-kinase (PI3K)/AKT mitogen...
Despite progress in systemic small interfering RNA (siRNA) delivery to the liver and solid tumors, siRNA leukocytes remains challenging. The ability silence gene expression has great potential for identifying drug targets RNAi-based therapy leukocyte diseases. However, both normal malignant are among most difficult as they resistant conventional transfection reagents dispersed body. We used mantle cell lymphoma (MCL) a prototypic blood cancer validating novel strategy. MCL is an aggressive...
Abstract Lasting B cell persistence depends on survival signals that are transduced by surface receptors. In this study, we describe a novel biological mechanism essential for and homeostasis of normal peripheral mature cells chronic lymphocytic leukemia cells, regulated the heparin-binding cytokine, midkine (MK), its proteoglycan receptor, receptor-type tyrosine phosphatase ζ (RPTPζ). We demonstrate MK initiates signaling cascade leading to binding RPTPζ. mice lacking PTPRZ, proportion...
Abstract NF-κB plays a major role in the pathogenesis of B-cell neoplasms. A broad array mostly extracellular stimuli has been reported to activate NF-κB, various degrees, chronic lymphocytic leukemia (CLL) cells. Because CLL cells harbor high levels unphosphorylated STAT-3 (USTAT-3) and USTAT-3 was we sought determine whether activates CLL. Using electrophoretic mobility shift assay (EMSA), studied peripheral blood low-density from 15 patients with found that cell nuclear extracts all...
Locked nucleic acids (LNAs) are a subtype of antisense oligonucleotides (ASOs) that characterized by bridge within the sugar moiety. LNAs owe their robustness to this chemical modification, which as name suggests, locks it in one conformation. This perspective includes two components: general overview on ASOs from side and delivery issues focusing lipid nanoparticles (LNPs) other side. Throughout, screening ongoing clinical trials involving is given, well take versatility challenges using...
The potential of microtubule-associated protein targets for cancer therapeutics remains largely unexplored due to the lack target-specific agents. Here, we explored therapeutic targeting cytoskeleton-associated 5 (CKAP5), an important protein, with CKAP5-targeting siRNAs encapsulated in lipid nanoparticles (LNPs). Our screening 20 solid cell lines demonstrated selective vulnerability genetically unstable response CKAP5 silencing. We identified a highly responsive chemo-resistant ovarian...
Immunotherapy has a great potential in advancing cancer treatment especially light of recent discoveries and therapeutic interventions that lead to complete response specific subgroups melanoma patients. By using the body's own immune system it is possible not only specifically target eliminate cells while leaving healthy unharmed, but also elicit long-term protective response. Despite promise, current immunotherapy limited fails addressing all tumor types. This probably due fact single...
Abstract Yersinia pestis , the causative agent of plague, remains a significant global health hazard and potential top‐tier biothreat despite modern medical advances. Here, two mRNA constructs encoding different versions low‐calcium response virulence (LcrV) protective antigen, an essential factor Y. are designed evaluated. Next, immunogenicity efficacy both independently in combination is assessed with previously reported F1‐encoding construct well‐established mouse model pneumonic plague....