Molecular Transducers for Biomedical Applications Molecular Transducers for Biomedical

Molecular Transducers for Biomedical Applications Molecular Transducers for Biomedical Applications NanoMedica, Inc. August 12, 2004 creating better medicine through nanotechnology NanoMedica, Inc. Workshop on MicroManufacturing, NSF, August 12, 2004 Molecular Transducers for Biomedical Applications NanoMedica, Inc. Developing single-molecule techniques for molecular detection, discovery & delivery Distance 15 nm above slide 10 nm 5 nm Nanobead Acceptor Donor FRET signal Target Aptamer n tio ita c Ex Microscope slide TIR illumination Microscope objective Workshop on MicroManufacturing, NSF, August 12, 2004 NanoMedica, Inc. 1 Molecular Transducers for Biomedical Applications SmartDrug™ Production & Delivery Production + Drug molecules Synthetic receptor (chaperone) High-capacity smaRTdrug™ complex Target-dependent drug release Delivery Therapeutic target GOAL: Designed control of (bio)molecular transduction NanoMedica, Inc. Workshop on MicroManufacturing, NSF, August 12, 2004 Molecular Transducers for Biomedical Applications NanoDiscovery Platform 1) NanoSelection method 2) NanoAssembly of dual action smaRTdrugs™ o o + + o o 3) smaRTdrug™ delivery to cancer target o o NanoMedica, Inc. Workshop on MicroManufacturing, NSF, August 12, 2004 2 Molecular Transducers for Biomedical Applications Structural & Functional Benefits Compact size: Greater tumor penetration & cancer cell kill Defined composition: Improved safety, efficacy and product quality Nonimmunogenic: No need to humanize (unlike monoclonals) Dual-specificity & dual-action NanoAssembled construct Monoclonal antibody o o o o o o (Multiple drugs per construct) (Single drug molecule) NanoMedica, Inc. Workshop on MicroManufacturing, NSF, August 12, 2004 Molecular Transducers for Biomedical Applications Single-Molecule “NanoSelection Process” Diverse library (>1012 members) Bind & wash Immobilized target molecules Detect & measure Force spectroscopy Determine affinity Isolate BENEFITS: Diversity space Speed to lead Cost to clinical Time to market Identify & characterize single ligand molecules NanoMedica, Inc. Workshop on MicroManufacturing, NSF, August 12, 2004 3 Molecular Transducers for Biomedical Applications Goal of NanoSelection Process Monday Detect & isolate new ligands Tuesday Wednesday Thursday Friday Identify ligands Pilot scale-up, purification, QC Assay & characterization New genomic target New drug candidate Workshop on MicroManufacturing, NSF, August 12, 2004 NanoMedica, Inc. Molecular Transducers for Biomedical Applications Drug Discovery Process: Finding a New Lead Current 10,000-500,000 candidates 2 years Goal of NanoSelection Process 100,000,000,000,000 candidates 5 days • NanoMedica Number of Compounds Current x Time NanoMedica, Inc. Workshop on MicroManufacturing, NSF, August 12, 2004 4 Molecular Transducers for Biomedical Applications NanoAssembly Process Self-assembly of bivalent targeting ligand 1st selected ligand + 2nd selected ligand Bivalent targeting ligand o o Self-assembly of dual-action smaRTdrug™ + o o Bivalent Targeting ligand smaRTdrug™ payload delivery components Dual-Action therapeutic (targeted release smaRTdrug™) NanoMedica, Inc. Workshop on MicroManufacturing, NSF, August 12, 2004 Molecular Transducers for Biomedical Applications Bioderived Supramolecular Transducers Light-harvesting antenna structures from red & blue-green algae 50 – 80 nm NanoMedica, Inc. Workshop on MicroManufacturing, NSF, August 12, 2004 5 Molecular Transducers for Biomedical Applications Molecular Transducer Properties PBXL (SensiLight™) Dyes 250 – 600 nm Engineered light-harvesting antennae PE PE PE PE PE PE PE PE PE PE PE PE PE PE APC PC P APC APC PC PE PE PE PC PE PC PE PE PE PE PE PE Stable, bioderived nanodevices Functionally soluble Large Stokes shift (near-IR emission) 100x brighter than Quantum Dots™ APC PE PE PE PE PE PE PC APC PC PE PE PE PE PE PE APC 666 nm NanoMedica, Inc. Workshop on MicroManufacturing, NSF, August 12, 2004 Molecular Transducers for Biomedical Applications Transducer Function Performance in DNA array (vs. R-PE) 8000 RFU PBXL-1 Spectral Properties 16 Relative Fluorescence Excitation 12 8 Emission PBXL-1 6000 4000 2000 4 0 0 R-PE 450 550 650 750 Wavelength (nm) 0 2 4 6 8 [oligo] (fmol) 10 12 14 NanoMedica, Inc. Workshop on MicroManufacturing, NSF, August 12, 2004 6 Molecular Transducers for Biomedical Applications State-of-the-Art: Molecular Transducers Function Molecular writing Molecular detection Nucleic acid detection Nucleic acid detection Protein detection Molecular switch, protein signaling Modulation of signal transduction Modulation of signal transduction Application Research & development Drug discovery, arrays, diagnostics In vitro genomics, diagnostics In vitro & cellbased genomics Drug discovery, life sciences research Drug delivery, therapeutics Therapy - cancers Therapy – macular degeneration Technology Dip-pen nanolithography Light-harvesting antenna structures Probe-modified gold nanoparticles Nucleotide-based molecular switch Fluorescent fusion proteins Fusion-based protein interaction Monoclonal antibody Oligonucleotide ligand (aptamer) Institution NanoInk Martek Nanosphere Public Health Research Institute Aurora (Amersham) Johns Hopkins Genentech Imclone EyeTech (Pfizer) Product NSCRIPTOR™ DPNWriter Superfluors™, SensiLight™ dyes Verigene™ platform Molecular Beacons GFPs Research stage Herceptin Erbitux Macugen™ NanoMedica, Inc. Workshop on MicroManufacturing, NSF, August 12, 2004 Molecular Transducers for Biomedical Applications Scientific Barrier Understanding at molecular and submolecular scale the relationship among sequence, structure and function for biological, biomimetic & bioinspired molecules and materials. NanoMedica, Inc. Workshop on MicroManufacturing, NSF, August 12, 2004 7 Molecular Transducers for Biomedical Applications Technological Barrier Operative attachment of complex molecules to nanoscale, microscale and/or macroscale devices without impairing molecular and/or device function. NanoMedica, Inc. Workshop on MicroManufacturing, NSF, August 12, 2004 Molecular Transducers for Biomedical Applications Commercial Barriers Identifying the customer Finding out what the customer wants Providing it NanoMedica, Inc. Workshop on MicroManufacturing, NSF, August 12, 2004 8