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Localized optical control of therapeutic gene release

YGTLC Annual Meeting, January 5-7, 2006. Localized optical control of therapeutic gene release. Eunice S. Lee, Gang L. Liu, Franklin J. Kim, Yitao Long, and Luke P. Lee Biomolecular Nanotechnology Center Berkeley Sensor & Actuator Center Department of Bioengineering. Outline.

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Localized optical control of therapeutic gene release

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  1. YGTLC Annual Meeting, January 5-7, 2006 Localized optical control of therapeutic gene release Eunice S. Lee, Gang L. Liu, Franklin J. Kim, Yitao Long, and Luke P. Lee Biomolecular Nanotechnology Center Berkeley Sensor & Actuator Center Department of Bioengineering

  2. Outline • Motivation of ONCOs* • Design of ONCOs* • Characterizations of ONCOs* • Conclusions * ONCOs: Oligonucleotides on Nanoplasmonic Carrier-based Optical Switch

  3. Clinical application: Gene Therapy • Introduction of genes can be used to control expression of proteins • 30% of breast cancers overexpress HER-2 protein • Excess HER-2 protein promotes growth of cancer cells

  4. DNA RNA protein AAAA AAAA AAAA RNA + short dna short dna Gene Release Therapy cell Genetic Code: DNA => RNA => protein • Therapy: Short dna bind to RNA to stop production of protein. • Targets proteins in cancer translate protein transcribe nucleus Nanotechnology!

  5. red blood cells penny nanoparticles 50 nm !! micrometer (10-6 m) 1.4 millimeters (10-3 m) nanometers (10-9 m) Nanoparticles as Carriers Why nano? • Materials have new properties in nanoscale • Need new tools that are the same size as cells

  6. Concept of ONCOS therapeutic gene • Protective delivery vehicle • Localized optical activation • Selective near infrared activation • Low temperature activation ONCOS activation therapeutic genes released ONCOS activated nanoparticle

  7. Concept of ONCOS therapy therapeutic gene binds to mRNA Cell ONCOS activation degraded mRNA nucleus mRNA nanoparticles protein translated activated nanoparticle inactivated nanoparticle

  8. After laser excitation Before Immobilized nanoparticles in solution Localized Optical Activation ONCOS activation dye Nanoparticles immobilized on glass

  9. Localized Optical Activation in cells cell activated nanoparticle ONCOS activation nucleus Nanoparticles (dna dyed green) unactivated nanoparticle After activation Before nucleus cytosol activated nanoparticles breast cancer cells unactivated nanoparticles nucleus

  10. unbound dye Treated cell Treated activated nanoparticles 10 mm 10 mm HER-2 protein blocked Untreated cell Control dye HER-2

  11. Conclusions • Oligonucleotides on Nanoplasmonic Carrier-based Optical Switch (ONCOs) is designed. • Selective optical activation of ONCOs is established. • Localized & low temperature optical activation is demonstrated by ONCOs. • Inhibition of HER-2 protein by ONCOs is verified for cancer therapy applications.

  12. Acknowledgments • Undergraduate students : Shalini Indrakanti Angelee Kumar Tran Ta • Technical expertise: Megan Dueck Terry Johnson • Research Funding: National Physical Science Consortium (NPSC) graduate fellowship Biopoets’ website:http://biopoems.berkeley.edu

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