The Experts below are selected from a list of 7497 Experts worldwide ranked by ideXlab platform
Daniel G Anderson - One of the best experts on this subject based on the ideXlab platform.
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bioinspired alkenyl amino alcohol ionizable lipid materials for highly potent in vivo mrna Delivery
Advanced Materials, 2016Co-Authors: Owen S Fenton, Robert Langer, Kevin J Kauffman, Rebecca L Mcclellan, Eric A Appel, Robert J Dorkin, Mark W Tibbitt, Michael W Heartlein, Frank Derosa, Daniel G AndersonAbstract:Thousands of human diseases could be treated by selectively controlling the expression of specific proteins in vivo. A new series of alkenyl amino alcohol (AAA) ionizable lipid nanoparticles (LNPs) capable of delivering human mRNA with unprecedented levels of in vivo efficacy is demonstrated. This study highlights the importance of utilizing synthesis tools in tandem with biological inspiration to understand and improve Nucleic Acid Delivery in vivo.
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lipidoid coated iron oxide nanoparticles for efficient dna and sirna Delivery
Nano Letters, 2013Co-Authors: Shan Jiang, Ahmed A Eltoukhy, Kevin T Love, Robert Langer, Daniel G AndersonAbstract:The safe, targeted and effective Delivery of gene therapeutics remains a significant barrier to their broad clinical application. Here we develop a magnetic Nucleic Acid Delivery system composed of iron oxide nanoparticles and cationic lipid-like materials termed lipidoids. Coated nanoparticles are capable of delivering DNA and siRNA to cells in culture. The mean hydrodynamic size of these nanoparticles was systematically varied and optimized for Delivery. While nanoparticles of different sizes showed similar siRNA Delivery efficiency, nanoparticles of 50–100 nm displayed optimal DNA Delivery activity. The application of an external magnetic field significantly enhanced the efficiency of Nucleic Acid Delivery, with performance exceeding that of the commercially available lipid-based reagent, Lipofectamine 2000. The iron oxide nanoparticle Delivery platform developed here offers the potential for magnetically guided targeting, as well as an opportunity to combine gene therapy with MRI imaging and magnetic ...
Theresa M. Reineke - One of the best experts on this subject based on the ideXlab platform.
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poly 2 deoxy 2 methacrylamido glucopyranose b poly methacrylate amine s optimization of diblock glycopolycations for Nucleic Acid Delivery
ACS Macro Letters, 2013Co-Authors: Mallory Cortez, Haley R Phillips, Theresa M. ReinekeAbstract:A series of nine poly(2-deoxy-2-methacrylamido glucopyranose)-b-poly(methacrylate amine) diblock copolycations has been synthesized as new colloidally stable polynucleotide vehicles. The cationic block was varied in length and in the degree of methyl group substitution (secondary, tertiary, quaternary) on the pendant amine in an effort to optimize the structure and activity for plasmid DNA (pDNA) Delivery. Upon a thorough kinetic study of polymerization for each polymer, the glycopolymers were prepared with well-controlled Mn and Đ. The binding and colloidal stability of the polymer–pDNA nanocomplexes at different N/P ratios and in biological media have been investigated using gel electrophoresis and light scattering techniques. The toxicity and transfection efficiency of the polyplexes have been evaluated with Hep G2 (human liver hepatocellular carcinoma) cells; several polymers displayed excellent Delivery and toxicity profiles justifying their further development for in vivo gene therapy.
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theranostics combining imaging and therapy
Bioconjugate Chemistry, 2011Co-Authors: Sneha S Kelkar, Theresa M. ReinekeAbstract:Employing theranostic nanoparticles, which combine both therapeutic and diagnostic capabilities in one dose, has promise to propel the biomedical field toward personalized medicine. This review presents an overview of different theranostic strategies developed for the diagnosis and treatment of disease, with an emphasis on cancer. Herein, therapeutic strategies such as Nucleic Acid Delivery, chemotherapy, hyperthermia (photothermal ablation), photodynamic, and radiation therapy are combined with one or more imaging functionalities for both in vitro and in vivo studies. Different imaging probes, such as MRI contrast agents (T1 and T2 agents), fluorescent markers (organic dyes and inorganic quantum dots), and nuclear imaging agents (PET/SPECT agents), can be decorated onto therapeutic agents or therapeutic Delivery vehicles in order to facilitate their imaging and, in so doing, gain information about the trafficking pathway, kinetics of Delivery, and therapeutic efficacy; several such strategies are outline...
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polycationic β cyclodextrin click clusters monodisperse and versatile scaffolds for Nucleic Acid Delivery
Journal of the American Chemical Society, 2008Co-Authors: Sathya Srinivasachari, Katye M Fichter, Theresa M. ReinekeAbstract:Herein, a novel series of multivalent polycationic β-cyclodextrin “click clusters” with discrete molecular weight have been synthesized, characterized, and examined as therapeutic pDNA carriers. The materials were creatively designed based on a β-cyclodextrin core to impart a biocompatible multivalent architecture and oligoethyleneamine arms to facilitate pDNA binding, encapsulation, and cellular uptake. An acetylated-per-azido-β-cyclodextrin (4) was reacted with series of alkyne dendrons (7a−e) (containing one to five ethyleneamine units) using copper-catalyzed 1,3-dipolar cycloaddition, to form a series of click clusters (9a−e) bearing 1,2,3-triazole linkers. Gel electrophoresis experiments, dynamic light scattering, and transmission electron microscopy revealed that the macromolecules bind and compact pDNA into spherical nanoparticles in the size range of 80−130 nm. The polycations protect pDNA against nuclease degradation, where structures 9c, 9d, and 9e did not allow pDNA degradation in the presence ...
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peptide functionalized poly ethylene glycol star polymers dna Delivery vehicles with multivalent molecular architecture
Bioconjugate Chemistry, 2008Co-Authors: Katye M Fichter, Le Zhang, Kristi L Kiick, Theresa M. ReinekeAbstract:Exploring the development of nonviral Nucleic Acid Delivery vectors with progressive, specific, and novel designs in molecular architecture is a fundamental way to investigate how aspects of chemical and physical structure impact the transfection process. In this study, macromolecules comprised of a four-arm star poly(ethylene glycol) and termini modified with one of five different heparin binding peptides have been investigated for their ability to bind, compact, and deliver DNA to mammalian cells in vitro. These new Delivery vectors combine a PEG-derived stabilizing moiety with peptides that exhibit unique cell-surface binding ability in a molecular architecture that permits multivalent presentation of the cationic peptides. Five peptide sequences of varying heparin binding affinity were studied; each was found to sufficiently bind heparin for biological application. Additionally, the macromolecules were able to bind and compact DNA into particles of proper size for endocytosis. In biological studies, t...
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deciphering the role of hydrogen bonding in enhancing pdna polycation interactions
Langmuir, 2007Co-Authors: Lisa E Prevette, Theresa M. Reineke, Thomas E Kodger, Matthew Lawrence LynchAbstract:There is considerable interest in the binding and condensation of DNA with polycations to form polyplexes because of their possible application to cellular Nucleic Acid Delivery. This work focuses on studying the binding of plasmid DNA (pDNA) with a series of poly(glycoamidoamine)s (PGAAs) that have previously been shown to deliver pDNA in vitro in an efficient and nontoxic manner. Herein, we examine the PGAA−pDNA binding energetics, binding-linked protonation, and electrostatic contribution to the free energy with isothermal titration calorimetry (ITC). The size and charge of the polyplexes at various ITC injection points were then investigated by light scattering and ζ-potential measurements to provide comprehensive insight into the formation of these polyplexes. An analysis of the calorimetric data revealed a three-step process consisting of two different endothermic contributions followed by the condensation/aggregation of polyplexes. The strength of binding and the point of charge neutralization were...
Christian Plank - One of the best experts on this subject based on the ideXlab platform.
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magnetically enhanced Nucleic Acid Delivery ten years of magnetofection progress and prospects
Advanced Drug Delivery Reviews, 2011Co-Authors: Christian Plank, Olivier Zelphati, Olga MykhaylykAbstract:Nucleic Acids carry the building plans of living systems. As such, they can be exploited to make cells produce a desired protein, or to shut down the expression of endogenous genes or even to repair defective genes. Hence, Nucleic Acids are unique substances for research and therapy. To exploit their potential, they need to be delivered into cells which can be a challenging task in many respects. During the last decade, nanomagnetic methods for delivering and targeting Nucleic Acids have been developed, methods which are often referred to as magnetofection. In this review we summarize the progress and achievements in this field of research. We discuss magnetic formulations of vectors for Nucleic Acid Delivery and their characterization, mechanisms of magnetofection, and the application of magnetofection in viral and nonviral Nucleic Acid Delivery in cell culture and in animal models. We summarize results that have been obtained with using magnetofection in basic research and in preclinical animal models. Finally, we describe some of our recent work and end with some conclusions and perspectives.
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Generation of magnetic nonviral gene transfer agents and magnetofection in vitro.
Nature protocols, 2007Co-Authors: Olga Mykhaylyk, Dialechti Vlaskou, Yolanda Sánchez Antequera, Christian PlankAbstract:This protocol details how to design and conduct experiments to deliver Nucleic Acids to adherent and suspension cell cultures in vitro by magnetic force-assisted transfection using self-assembled complexes of Nucleic Acids and cationic lipids or polymers (nonviral gene vectors), which are associated with magnetic (nano) particles. These magnetic complexes are sedimented onto the surface of the cells to be transfected within minutes by the application of a magnetic gradient field. As the diffusion barrier to Nucleic Acid Delivery is overcome, the full vector dose is targeted to the cell surface and transfection is synchronized. In this manner, the transfection process is accelerated and transfection efficiencies can be improved up to several 1,000-fold compared with transfections carried out with nonmagnetic gene vectors. This protocol describes how to accomplish the following stages: synthesis of magnetic nanoparticles for magnetofection; testing the association of DNA with the magnetic components of the transfection complex; preparation of magnetic lipoplexes and polyplexes; magnetofection; and data processing. The synthesis and characterization of magnetic nanoparticles can be accomplished within 3-5 d. Cell culture and transfection is then estimated to take 3 d. Transfected gene expression analysis, cell viability assays and calibration will probably take a few hours. This protocol can be used for cells that are difficult to transfect, such as primary cells, and may also be applied to viral Nucleic Acid Delivery. With only minor alterations, this protocol can also be useful for magnetic cell labeling for cell tracking studies and, as it is, will be useful for screening vector compositions and novel magnetic nanoparticle preparations for optimized transfection efficiency in any cell type.
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advances in magnetofection magnetically guided Nucleic Acid Delivery
Journal of Magnetism and Magnetic Materials, 2005Co-Authors: Ulrike Schillinger, Christian Bergemann, Florian Krotz, Carsten Rudolph, J Hirschberger, T Brill, Stephanie Huth, Soren W Gersting, Christian PlankAbstract:Magnetofection is Nucleic Acid Delivery to cells supported and site-specifically guided by the attractive forces of magnetic fields acting on Nucleic Acid shuttles (vectors) which are associated with magnetic nanoparticles. Recent progress with the method confirms its general applicability with small and large Nucleic Acids and viruses. The method's therapeutic application as well as mechanistic studies will be discussed.
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enhancing and targeting Nucleic Acid Delivery by magnetic force
Expert Opinion on Biological Therapy, 2003Co-Authors: Christian Plank, Carsten Rudolph, Martina Anton, Joseph Rosenecker, Florian KrotzAbstract:Insufficient contact of inherently highly active Nucleic Acid Delivery systems with target cells is a primary reason for their often observed limited efficacy. Physical methods of targeting can overcome this limitation and reduce the risk of undesired side effects due to non-target site Delivery. The authors and others have developed a novel means of physical targeting, exploiting magnetic force acting on Nucleic Acid vectors associated with magnetic particles in order to mediate the rapid contact of vectors with target cells. Here, the principles of magnetic drug and Nucleic Acid Delivery are reviewed, and the facts and potentials of the technique for research and therapeutic applications are discussed. Magnetically enhanced Nucleic Acid Delivery - magnetofection - is universally applicable to viral and non-viral vectors, is extraordinarily rapid, simple and yields saturation level transfection at low dose in vitro. The method is useful for site-specific vector targeting in vivo. Exploiting the full potential of the technique requires an interdisciplinary research effort in magnetic field physics, magnetic particle chemistry, pharmaceutical formulation and medical application.
Evelyne Jouvinmarche - One of the best experts on this subject based on the ideXlab platform.
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tuning the immunostimulation properties of cationic lipid nanocarriers for Nucleic Acid Delivery
Frontiers in Immunology, 2021Co-Authors: Arindam K. Dey, Adrien Nougarède, Flora Clément, Carole Fournier, Evelyne JouvinmarcheAbstract:Nonviral systems, such as lipid nanoparticles, have emerged as reliable methods to enable Nucleic Acid intracellular Delivery. The use of cationic lipids in various formulations of lipid nanoparticles enables the formation of complexes with Nucleic Acid cargo and facilitates their uptake by target cells. However, due to their small size and highly charged nature, these nanocarrier systems can interact in vivo with antigen-presenting cells (APCs), such as dendritic cells (DCs) and macrophages. As this might prove to be a safety concern for developing therapies based on lipid nanocarriers, we sought to understand how they could affect the physiology of APCs. In the present study, we investigate the cellular and metabolic response of primary macrophages or DCs exposed to the neutral or cationic variant of the same lipid nanoparticle formulation. We demonstrate that macrophages are the cells affected most significantly and that the cationic nanocarrier has a substantial impact on their physiology, depending on the positive surface charge. Our study provides a first model explaining the impact of charged lipid materials on immune cells and demonstrates that the primary adverse effects observed can be prevented by fine-tuning the load of Nucleic Acid cargo. Finally, we bring rationale to calibrate the Nucleic Acid load of cationic lipid nanocarriers depending on whether immunostimulation is desirable with the intended therapeutic application, for instance, gene Delivery or messenger RNA vaccines.
Robert Langer - One of the best experts on this subject based on the ideXlab platform.
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Lipidoid-coated Iron Oxide Nanoparticles for Efficient DNA and siRNA Delivery
2016Co-Authors: Shan Jiang, Ahmed A Eltoukhy, Kevin T Love, Robert Langer, Daniel GAbstract:The safe, targeted and effective Delivery of gene therapeutics remains a significant barrier to their broad clinical application. Here we develop a magnetic Nucleic Acid Delivery system composed of iron oxide nanoparticles and cationic lipid-like materials termed lipidoids. Coated nanoparticles are capable of delivering DNA and siRNA to cells in culture. The mean hydrodynamic size of these nanoparticles was systematically varied and optimized for Delivery. While nanoparticles of different sizes showed similar siRNA Delivery efficiency, nanoparticles of 50–100 nm displayed optimal DNA Delivery activity. The application of an external magnetic field significantly enhanced the efficiency of Nucleic Acid Delivery, with performance exceeding that of the commercially available lipid-based reagent, Lipofectamine 2000. The iron oxide nanoparticle Delivery platform developed here offers the potential for magnetically guided targeting, as well as an opportunity to combine gene therapy with MRI imaging and magnetic hyperthermia. Keywords siRNA Delivery; DNA Delivery; iron oxide nanoparticle; magnetofection; gene therapy Gene therapy has the potential to treat a broad range of human diseases1. However, the mai
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bioinspired alkenyl amino alcohol ionizable lipid materials for highly potent in vivo mrna Delivery
Advanced Materials, 2016Co-Authors: Owen S Fenton, Robert Langer, Kevin J Kauffman, Rebecca L Mcclellan, Eric A Appel, Robert J Dorkin, Mark W Tibbitt, Michael W Heartlein, Frank Derosa, Daniel G AndersonAbstract:Thousands of human diseases could be treated by selectively controlling the expression of specific proteins in vivo. A new series of alkenyl amino alcohol (AAA) ionizable lipid nanoparticles (LNPs) capable of delivering human mRNA with unprecedented levels of in vivo efficacy is demonstrated. This study highlights the importance of utilizing synthesis tools in tandem with biological inspiration to understand and improve Nucleic Acid Delivery in vivo.
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lipidoid coated iron oxide nanoparticles for efficient dna and sirna Delivery
Nano Letters, 2013Co-Authors: Shan Jiang, Ahmed A Eltoukhy, Kevin T Love, Robert Langer, Daniel G AndersonAbstract:The safe, targeted and effective Delivery of gene therapeutics remains a significant barrier to their broad clinical application. Here we develop a magnetic Nucleic Acid Delivery system composed of iron oxide nanoparticles and cationic lipid-like materials termed lipidoids. Coated nanoparticles are capable of delivering DNA and siRNA to cells in culture. The mean hydrodynamic size of these nanoparticles was systematically varied and optimized for Delivery. While nanoparticles of different sizes showed similar siRNA Delivery efficiency, nanoparticles of 50–100 nm displayed optimal DNA Delivery activity. The application of an external magnetic field significantly enhanced the efficiency of Nucleic Acid Delivery, with performance exceeding that of the commercially available lipid-based reagent, Lipofectamine 2000. The iron oxide nanoparticle Delivery platform developed here offers the potential for magnetically guided targeting, as well as an opportunity to combine gene therapy with MRI imaging and magnetic ...
