Research Topics
| Mark E DavisSummaryAffiliation: California Institute of Technology Country: USA Publications
Research Grants
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Detail Information
Publications
Polycation-siRNA nanoparticles can disassemble at the kidney glomerular basement membraneJonathan E Zuckerman
Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA
Proc Natl Acad Sci U S A 109:3137-42. 2012..This clearance mechanism may affect any nanoparticles that assemble primarily by electrostatic interactions between cationic delivery components and anionic nucleic acids (or other therapeutic entities)...
Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticlesMark E Davis
Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA
Nature 464:1067-70. 2010..Together, these data demonstrate that siRNA administered systemically to a human can produce a specific gene inhibition (reduction in mRNA and protein) by an RNAi mechanism of action...
Cyclodextrin-based pharmaceutics: past, present and futureMark E Davis
Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA
Nat Rev Drug Discov 3:1023-35. 2004..Cyclodextrin-containing polymers are reviewed and their use in drug delivery presented. Of specific interest is the use of cyclodextrin-containing polymers to provide unique capabilities for the delivery of nucleic acids...
Self-assembling nucleic acid delivery vehicles via linear, water-soluble, cyclodextrin-containing polymersM E Davis
Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA
Curr Med Chem 11:179-97. 2004..This vehicle is the first example of a polymer-based gene delivery system formed entirely by self-assembly...
Nanoparticle therapeutics: an emerging treatment modality for cancerMark E Davis
Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA
Nat Rev Drug Discov 7:771-82. 2008....
Design and development of IT-101, a cyclodextrin-containing polymer conjugate of camptothecinMark E Davis
Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA
Adv Drug Deliv Rev 61:1189-92. 2009..IT-101 is currently being investigated in human clinical trials. Here, the design and development of IT-101 is described with emphasis on features distinguishing it from other polymer-containing therapeutics...
Structural effects of carbohydrate-containing polycations on gene delivery. 2. Charge center typeTheresa M Reineke
Division of Chemistry, California Institute of Technology, Pasadena, California 91125, USA
Bioconjug Chem 14:255-61. 2003..Additionally, transfection experiments conducted in the presence of chloroquine reveal increased gene expression from quaternary ammonium containing polycations and not from their amidine analogues...
The first targeted delivery of siRNA in humans via a self-assembling, cyclodextrin polymer-based nanoparticle: from concept to clinicMark E Davis
California Institute of Technology, Pasadena, California 91125, USA
Mol Pharm 6:659-68. 2009..The four component formulation is self-assembled into nanoparticles in the pharmacy and administered intravenously (iv) to patients. The designed features of this experimental therapeutic are described, and their functions illustrated...
Ordered porous materials for emerging applicationsMark E Davis
Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA
Nature 417:813-21. 2002..In fact, porous materials now seem set to contribute to developments in areas ranging from microelectronics to medical diagnosis...
Non-viral gene delivery systemsMark E Davis
Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA
Curr Opin Biotechnol 13:128-31. 2002..In vivo, problems of extracellular non-specific interactions and intracellular trafficking to the nucleus are also encountered. Recent progress has been made in overcoming these issues...
Structure-function correlation of chloroquine and analogues as transgene expression enhancers in nonviral gene deliveryJianjun Cheng
Insert Therapeutics, 2585 Nina Street, Pasadena, CA 91107, USA
J Med Chem 49:6522-31. 2006....
Physicochemical and biological characterization of targeted, nucleic acid-containing nanoparticlesDerek W Bartlett
Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA
Bioconjug Chem 18:456-68. 2007..The analysis of the CDP delivery vehicle provides insights that can be applied to the design of targeted nucleic acid delivery vehicles in general...
Transferrin-containing, cyclodextrin polymer-based particles for tumor-targeted gene deliveryNathalie C Bellocq
Insert Therapeutics, Inc, Pasadena, California, USA
Bioconjug Chem 14:1122-32. 2003..The transferrin-modified nanoparticles are appropriate for use in the systemic delivery of nucleic acid therapeutics for metastatic cancer applications...
Pharmacokinetics and tumor dynamics of the nanoparticle IT-101 from PET imaging and tumor histological measurementsThomas Schluep
Calando Pharmaceuticals, Inc, 129 North Hill Avenue, Pasadena, CA 91106, USA
Proc Natl Acad Sci U S A 106:11394-9. 2009..Histological measurements using confocal microscopy show that IT-101 localizes within tumor cells and provides the sink in the tumor for the nanoparticles...
Targeted delivery of RNA-cleaving DNA enzyme (DNAzyme) to tumor tissue by transferrin-modified, cyclodextrin-based particlesSuzie H Pun
Insert Therapeutics, Inc, Pasadena, California, USA
Cancer Biol Ther 3:641-50. 2004..Tumor cell uptake is observed with intravenous bolus injection only, and intracellular delivery requires transferrin targeting...
Cyclodextrin-modified polyethylenimine polymers for gene deliverySuzie H Pun
Insert Therapeutics Inc, 2585 Nina Street, Pasadena, California 91107, USA
Bioconjug Chem 15:831-40. 2004..Tail vein injections into mice of 120 microg of plasmid DNA formulated with CD-lPEI and AD-PEG do not reveal observable toxicities, and both nucleic acid accumulation and expression are observed in liver...
Preclinical efficacy of the camptothecin-polymer conjugate IT-101 in multiple cancer modelsThomas Schluep
Insert Therapeutics, Inc, Pasadena, CA 91107, USA
Clin Cancer Res 12:1606-14. 2006..Taken together, these results indicate that IT-101 has good tolerability and antitumor activity against a wide range of tumors...
Single cell kinetics of intracellular, nonviral, nucleic acid delivery vehicle acidification and traffickingRajan P Kulkarni
Option in Biochemistry and Molecular Biophysics, California Institute of Technology, Pasadena, California 91125, USA
Bioconjug Chem 16:986-94. 2005..Here, the live cell, spatiotemporal mapping of these behaviors is demonstrated and, when combined with cell uptake and luciferase expression data, shows that there is not a correlation between buffering capacity and gene expression...
Potent siRNA inhibitors of ribonucleotide reductase subunit RRM2 reduce cell proliferation in vitro and in vivoJeremy D Heidel
Calando Pharmaceuticals, Inc, California Institute of Technology, Pasadena, California 91107, USA
Clin Cancer Res 13:2207-15. 2007..Here, a potent small interfering RNA (siRNA) duplex against the M2 subunit of RR (RRM2) is developed and shown to reduce the growth potential of cancer cells both in vitro and in vivo...
Pharmacokinetics and biodistribution of the camptothecin-polymer conjugate IT-101 in rats and tumor-bearing miceThomas Schluep
Insert Therapeutics, Inc, 3525 Nina Street, Pasadena, CA, 91107, USA
Cancer Chemother Pharmacol 57:654-62. 2006..These effects likely play a significant role in the enhanced antitumor activity of IT-101 when compared to CPT alone or irinotecan...
Imidazole groups on a linear, cyclodextrin-containing polycation produce enhanced gene delivery via multiple processesSwaroop Mishra
Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA
J Control Release 116:179-91. 2006..Together, these data suggest that differences in transfection efficiency between CDP and CDPim result from factors beyond buffering activity and endosomal escape...
Effect of siRNA nuclease stability on the in vitro and in vivo kinetics of siRNA-mediated gene silencingDerek W Bartlett
Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA
Biotechnol Bioeng 97:909-21. 2007....
A nanoparticle-based model delivery system to guide the rational design of gene delivery to the liver. 1. Synthesis and characterizationStephen R Popielarski
Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA
Bioconjug Chem 16:1063-70. 2005..All four particles have the same surface charge, and Gal-50 and Gal-140 have the same surface galactose density. The availability of galactose ligands to receptor binding is demonstrated here by agglutination with RCA120...
Antitumor activity of beta-cyclodextrin polymer-camptothecin conjugatesJianjun Cheng
Insert Therapeutics, Inc, 2585 Nina Street, Pasadena, California 91107, USA
Mol Pharm 1:183-93. 2004....
PEGylation significantly affects cellular uptake and intracellular trafficking of non-viral gene delivery particlesSwaroop Mishra
Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA
Eur J Cell Biol 83:97-111. 2004....
Structural effects of carbohydrate-containing polycations on gene delivery. 1. Carbohydrate size and its distance from charge centersTheresa M Reineke
Division of Chemistry, California Institute of Technology, Pasadena, California 91125, USA
Bioconjug Chem 14:247-54. 2003..The absence of a carbohydrate in the polycation produces high toxicity. All carbohydrate polycations transfect BHK-21 cells to approximately the same level of gene expression...
Impact of tumor-specific targeting and dosing schedule on tumor growth inhibition after intravenous administration of siRNA-containing nanoparticlesDerek W Bartlett
Chemical Engineering, California Institute of Technology, 1200 E California Blvd, MC 210 41, Pasadena, California 91125, USA
Biotechnol Bioeng 99:975-85. 2008....
Mechanism of active targeting in solid tumors with transferrin-containing gold nanoparticlesChung Hang J Choi
Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA
Proc Natl Acad Sci U S A 107:1235-40. 2010..These results suggest that targeted nanoparticles can provide greater intracellular delivery of therapeutic agents to the cancer cells within solid tumors than their nontargeted analogs...
Administration in non-human primates of escalating intravenous doses of targeted nanoparticles containing ribonucleotide reductase subunit M2 siRNAJeremy D Heidel
Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, MC 210 41, Pasadena, CA 91125, USA
Proc Natl Acad Sci U S A 104:5715-21. 2007..Taken together, the data presented show that multiple, systemic doses of targeted nanoparticles containing nonchemically modified siRNA can safely be administered to non-human primates...
Impact of tumor-specific targeting on the biodistribution and efficacy of siRNA nanoparticles measured by multimodality in vivo imagingDerek W Bartlett
Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, MC 210 41, Pasadena, CA 91125, USA
Proc Natl Acad Sci U S A 104:15549-54. 2007..Optimization of internalization may therefore be key for the development of effective nanoparticle-based targeted therapeutics...
A biodegradable filament for controlled drug deliveryBrendan C Mack
Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, United States
J Control Release 139:205-11. 2009..The filaments are generally well tolerated by the rabbits. Filament failure occurs at 6-8 days within the rabbit eyes, essentially the same time to failure observed from in-vitro mechanical properties testing results...
Clinical developments in nanotechnology for cancer therapyJeremy D Heidel
Calando Pharmaceuticals, Pasadena, California, USA
Pharm Res 28:187-99. 2011..Additionally, we discuss recent advances in the understanding of ligand-based targeting of nanoparticles, such as on receptor avidity and selectivity...
Synthetic biocompatible cyclodextrin-based constructs for local gene delivery to improve cutaneous wound healingNathalie C Bellocq
Insert Therapeutics, Inc, 2585 Nina Street, Pasadena, California 91107, USA
Bioconjug Chem 15:1201-11. 2004..These in vitro results suggest that the synthetic constructs are suitable for in vivo tissue repair applications...
Insights into the kinetics of siRNA-mediated gene silencing from live-cell and live-animal bioluminescent imagingDerek W Bartlett
Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA
Nucleic Acids Res 34:322-33. 2006....
Molecular conjugatesJeremy Heidel
Chemical Engineering, 210-41, California Institute of Technology, Pasadena 91125, USA
Adv Biochem Eng Biotechnol 99:7-39. 2005..We discuss some of the difficulties involved in the assembly of a functioning delivery system for in vivo use...
Targeting kidney mesangium by nanoparticles of defined sizeChung Hang J Choi
Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA
Proc Natl Acad Sci U S A 108:6656-61. 2011..Because many diseases originate from this area of the kidney, our findings establish design criteria for constructing nanoparticle-based therapeutics for targeting diseases that involve the mesangium of the kidney...
Cooperative catalysis by silica-supported organic functional groupsEric L Margelefsky
Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA
Chem Soc Rev 37:1118-26. 2008..Particular attention is given to the effect of the spatial arrangement of these organic groups and recent developments in the spatial organization of multiple groups on the silica surface...
A nanoparticle-based model delivery system to guide the rational design of gene delivery to the liver. 2. In vitro and in vivo uptake resultsStephen R Popielarski
Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA
Bioconjug Chem 16:1071-80. 2005....
Tin-containing zeolites are highly active catalysts for the isomerization of glucose in waterManuel Moliner
Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA
Proc Natl Acad Sci U S A 107:6164-8. 2010....
Development of a nonviral gene delivery vehicle for systemic applicationSuzie Hwang Pun
Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA
Bioconjug Chem 13:630-9. 2002..Thus, surface modification of betaCDP-based polyplexes through the use of cyclodextrin/adamantane host/guest interactions endows the particles with properties appropriate for systemic application...
A solvent-free method for isotopically or radioactively labeling cyclodextrins and cyclodextrin-containing polymersRyan K Zeidan
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena California 91125, USA
Bioconjug Chem 17:1624-6. 2006..The method can be generalized for use with materials that contain nucleophiles other than alcohols, e.g., amines...
Structural effects of carbohydrate-containing polycations on gene delivery. 3. Cyclodextrin type and functionalizationStephen R Popielarski
Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA
Bioconjug Chem 14:672-8. 2003..Further, gamma-CD-based polycations are shown to be less toxic than otherwise identical beta-CD-based polycations...
Synthesis of linear, beta-cyclodextrin-based polymers and their camptothecin conjugatesJianjun Cheng
Insert Therapeutics, Inc, 2585 Nina Street, Pasadena, California 91107, USA
Bioconjug Chem 14:1007-17. 2003..The parent polymer 2e has very low toxicity to all cultured cells tested...
Nanotechnology and cancerJames R Heath
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA
Annu Rev Med 59:251-65. 2008..The goal of the presentation is to identify nanotherapeutic strategies that are designed to increase efficacy while simultaneously minimizing the toxic side effects commonly associated with cancer chemotherapies...
Quantitating intracellular transport of polyplexes by spatio-temporal image correlation spectroscopyRajan P Kulkarni
Option in Biochemistry and Molecular Biophysics, California Institute of Technology, Pasadena, CA 91125, USA
Proc Natl Acad Sci U S A 102:7523-8. 2005..These studies suggest that spatio-temporal ICS is a powerful technique for assessing the nature of intracellular motion and provides a quantitative tool to compare the transport of different objects within a living cell...
Organized surface functional groups: cooperative catalysis via thiol/sulfonic acid pairingEric L Margelefsky
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA
J Am Chem Soc 129:13691-7. 2007..This work clearly reveals the importance of nanoscale organization of two disparate functional groups on the surface of heterogeneous catalysts...
Effects of structure of beta-cyclodextrin-containing polymers on gene deliveryS J Hwang
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA
Bioconjug Chem 12:280-90. 2001..In vitro toxicity varied by 1 order of magnitude and the lowest toxicity is observed with betaCDP8. The LD40 of the betaCDP6 to mice is 200 mg/kg, making this polymer a promising agent for in vivo gene delivery applications...
Regeneration of rat sciatic nerve across a LactoSorb bioresorbable conduit with interposed short-segment nerve graftsPaul C Francel
Department of Neurosurgery, University of Oklahoma, Health Sciences Center, Oklahoma City, Oklahoma 73104, USA
J Neurosurg 99:549-54. 2003..This study was conducted to evaluate peripheral nerve regeneration through a conduit composed of a bioresorbable material (LactoSorb)...
Mechanical and dielectric properties of pure-silica-zeolite low-k materialsZijian Li
Department of Chemical and Environmental Engineering, University of California, Riverside, CA 92521, USA
Angew Chem Int Ed Engl 45:6329-32. 2006
Profile of Mark E. DavisFarooq Ahmed
Proc Natl Acad Sci U S A 104:20651-3. 2007
Research Grants
- Design of Gene Delivery System to Target HepatocytesMark Davis; Fiscal Year: 2007..The long-term objective of our proposal is to design and engineer a generalized, synthetic system for ultimately delivering nucleic acid-based therapeutics to hepatocytes in humans. ..
- A Novel Method of Nanoparticle Delivery to Brain by Targeting Ec-gp96Mark E Davis; Fiscal Year: 2010....
