207 results on '"Dan Peer"'
Search Results
202. Advances in RNAi Therapeutic Delivery to Leukocytes using Lipid Nanoparticles
- Author
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Dalit Landesman-Milo, Srinivas Ramishetti, and Dan Peer
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0301 basic medicine ,Small interfering RNA ,business.industry ,Process development ,Gene Transfer Techniques ,Pharmaceutical Science ,Inflammation ,Genetic Therapy ,medicine.disease_cause ,Lipids ,Viral infection ,Autoimmunity ,03 medical and health sciences ,030104 developmental biology ,RNA interference ,Immunology ,Cancer research ,Nanoparticles ,Medicine ,RNA Interference ,medicine.symptom ,business - Abstract
Small interfering RNAs (siRNAs) therapeutics has advanced into clinical trials for liver diseases and solid tumors, but remain a challenge for manipulating leukocytes fate due to lack of specificity and safety issues. Leukocytes ingest pathogens and defend the body through a complex network. They are also involved in the pathogeneses of inflammation, viral infection, autoimmunity and cancers. Modulating gene expression in leukocytes using siRNAs holds great promise to treat leukocyte-mediated diseases. Leukocytes are notoriously hard to transduce with siRNAs and are spread throughout the body often located deep in tissues, therefore developing an efficient systemic delivery strategy is still a challenge. Here, we discuss recent advances in siRNA delivery to leukocyte subsets such as macrophages, monocytes, dendritic cells and lymphocytes. We focus mainly on lipid-based nanoparticles (LNPs) comprised of new generation of ionizable lipids and their ability to deliver siRNA to primary or malignant leukocytes in a targeted manner. Special emphasis is made on LNPs targeted to subsets of leukocytes and we detail a novel microfluidic mixing technology that could aid in changing the landscape of process development of LNPs from a lab tool to a potential novel therapeutic modality.
203. Focus on RNA interference: from nanoformulations to in vivo delivery.
- Author
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Jeffery M Karp and Dan Peer
- Subjects
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RNA interference , *OLIGONUCLEOTIDES , *SMALL interfering RNA , *TRANSTHYRETIN , *INTERFERON receptors - Published
- 2018
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204. Molecular and Cellular Therapies: New challenges and opportunities
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Bryon E. Petersen, Xiangdong Wang, and Dan Peer
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Drug ,Economics and Econometrics ,Molecular therapy ,Journal ,business.industry ,media_common.quotation_subject ,Genetic enhancement ,Allosteric regulation ,Cellular therapy ,Cancer ,Forestry ,Disease ,medicine.disease ,Bioinformatics ,Molecular medicine ,Cell therapy ,Editorial ,Materials Chemistry ,Media Technology ,medicine ,business ,Gene ,media_common - Abstract
Gene therapy is suggested to be one of the most specific and efficient modulations for gene deficient diseases and extended to other diseases like cancer and inflammation, even though there are still challenges to be faced, such as specific and selective delivery, minimal to no toxicity, efficient metabolism, simplicity, and measurable efficiency. It is important to identify and validate drug-able disease-specific targets for molecular and cellular therapies, while it is equally important to have disease biomarkers to trace and define the biological effects of molecular and cellular therapies. The importance and significance of allostery in molecular and cellular therapies and “allosteric disease”, “allosteric effect”, and “allosteric drug” should be more carefully examined and validated. Cell therapy has been attracting an increasing amount of consideration in the development of new treatments for diseases. Molecular and Cellular Therapies (MCT) is a new, open-access journal, devoted to molecular mechanisms, preclinical and clinical research and development of gene-, peptide-, protein-, and cell-based therapies.
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205. Harnessing RNAi nanomedicine for precision therapy
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Dan Peer
- Subjects
0303 health sciences ,Small interfering RNA ,business.industry ,Targeted Nanoparticles ,Genetic enhancement ,Computational biology ,Review ,Precision medicine ,Bioinformatics ,3. Good health ,Holy Grail ,03 medical and health sciences ,0302 clinical medicine ,Nanomedicine ,RNA interference ,030220 oncology & carcinogenesis ,RNAi ,Drug delivery ,microRNA ,Medicine ,business ,siRNAs, Precision medicine ,030304 developmental biology - Abstract
Utilizing RNA interference as an innovative therapeutic strategy has an immense likelihood to generate novel concepts in precision medicine. Several clinical trials are on the way with some positive initial results. Yet, targeting of RNAi payloads such as small interfering RNAs (siRNAs), microRNA (miR) mimetic or anti-miR (antagomirs) into specific cell types remains a challenge. Major attempts are done for developing nano-sized carriers that could overcome systemic, local and cellular barriers. This progress report will focus on the recent advances in the RNAi world, detailing strategies of systemic passive tissue targeting and active cellular targeting, which is often considered as the holy grail of drug delivery.
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206. Triggered-release polymeric conjugate micelles for on-demand intracellular drug delivery.
- Author
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Yanwu Cao, Min Gao, Chao Chen, Aiping Fan, Ju Zhang, Deling Kong, Zheng Wang, Dan Peer, and Yanjun Zhao
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DRUG delivery systems ,NANOCARRIERS ,MICELLES ,POLYETHYLENE glycol ,POLYLACTIC acid ,ZETA potential - Abstract
Nanoscale drug delivery platforms have been developed over the past four decades that have shown promising clinical results in several types of cancer and inflammatory disorders. These nanocarriers carrying therapeutic payloads are maximizing the therapeutic outcomes while minimizing adverse effects. Yet one of the major challenges facing drug developers is the dilemma of premature versus on-demand drug release, which influences the therapeutic regiment, efficacy and potential toxicity. Herein, we report on redox-sensitive polymer-drug conjugate micelles for on-demand intracellular delivery of a model active agent, curcumin. Biodegradable methoxy poly(ethylene glycol)-poly(lactic acid) copolymer (mPEG-PLA) was conjugated with curcumin via a disulfide bond or ester bond (control), respectively. The self-assembled redox-sensitive micelles exhibited a hydrodynamic size of 115.6 ± 5.9 (nm) with a zeta potential of −10.6 ± 0.7 (mV). The critical micelle concentration was determined at 6.7 ± 0.4 (μg mL
−1 ). Under sink conditions with a mimicked redox environment (10 mM dithiothreitol), the extent of curcumin release at 48 h from disulfide bond-linked micelles was nearly three times higher compared to the control micelles. Such rapid release led to a lower half maximal inhibitory concentration (IC50 ) in HeLa cells at 18.5 ± 1.4 (μg mL−1 ), whereas the IC50 of control micelles was 41.0 ± 2.4 (μg mL−1 ). The cellular uptake study also revealed higher fluorescence intensity for redox-sensitive micelles. In conclusion, the redox-sensitive polymeric conjugate micelles could enhance curcumin delivery while avoiding premature release, and achieving on-demand release under the high glutathione concentration in the cell cytoplasm. This strategy opens new avenues for on-demand drug release of nanoscale intracellular delivery platforms that ultimately might be translated into pre-clinical and future clinical practice. [ABSTRACT FROM AUTHOR]- Published
- 2015
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207. Assessing cellular toxicities in fibroblasts upon exposure to lipid-based nanoparticles: a high content analysis approach.
- Author
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Leonardo J Solmesky, Michal Shuman, Meir Goldsmith, Miguel Weil, and Dan Peer
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FIBROBLASTS ,NANOPARTICLES ,LIPIDS ,DRUG delivery systems ,NUCLEIC acids ,CYTOKINES - Abstract
Lipid-based nanoparticles (LNPs) are widely used for the delivery of drugs and nucleic acids. Although most of them are considered safe, there is confusing evidence in the literature regarding their potential cellular toxicities. Moreover, little is known about the recovery process cells undergo after a cytotoxic insult. We have previously studied the systemic effects of common LNPs with different surface charge (cationic, anionic, neutral) and revealed that positively charged LNPs ((+)LNPs) activate pro-inflammatory cytokines and induce interferon response by acting as an agonist of Toll-like receptor 4 on immune cells. In this study, we focused on the response of human fibroblasts exposed to LNPs and their cellular recovery process. To this end, we used image-based high content analysis (HCA). Using this strategy, we were able to show simultaneously, in several intracellular parameters, that fibroblasts can recover from the cytotoxic effects of (+)LNPs. The use of HCA opens new avenues in understanding cellular response and nanotoxicity and may become a valuable tool for screening safe materials for drug delivery and tissue engineering. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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