biology 280s - advanced in dna nanomedicine
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Powerpoint presentation accompanying file 'Paper 280S - Advanced in Nanomedicine in Cancer Detection and Therapeutics'.TRANSCRIPT
DNA Nanotechnology
Dr. Tai-ping SunBiology 280S: Biotechnology & Genetic Engineering
Joshua Mendoza-EliasFall 2008
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OutlinePart 1 - The Fight Against Cancer
I. Cancer: Barriers to therapeuticsII. Cancer: Current Diagnostics & TherapeuticsIII. Definition of Nanotechnology
A. What it is isB. How it is made
V. Examples of early Nanotechnology
Part 2 - DNA as new NanotechnologyVI. Properties of DNAVII. Innovative uses of DNA-folding Pathways VIII. DiagnosticsIX. Drug releaseX. The Shape of Things to Come
CancerClinical Manifestation:
-Uncontrolled cell proliferation-Loss of apoptosis-Growth Factors/Anti-Growth Factors-Angiogenesis-Invasion/metatases
Damage to somatic cell genome:-Oncogenes-Tumor suppressors-DNA replication errors-Epigenetics
Cancer: Barriers to Treatment. Immune System Surveillance
A. Self-antigenB. Clonal Evolution
. Tumour structures
. Cancer is “unique”
. Damage to healthy cells
Standing Order: Diagnostics & TherapeuticsDiagnostics:
• Location• Histology• Stage
Treatments:• Surgery• Chemotherapy• Radiotherapy• Targeted Therapy• Immunotherapy• Hormonal Therapy
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In situ: Breast Cancer tissue 400x
State of the Art: Cancer Nanotechnology
DetectionTreatment
DNA Microarrays
Bio “Finger”
Nanoparticles
Nanoparticles
Earlier detectionBetter Targeting
Imaging
Receptor Mediated
Lab on Chip
RadiationActivated
Gene based
Metabolicbased
Tissue Engineering
Cells
GF
scaffolding
Cancer Nanotechnology: Detection
Bio “Finger”
Cancer Nanotechnology: Treatment
Cancer Nanotechnology: Treatment continued . . .
Movie: National Cancer Institute
NCI Alliance for Nanotechnology in Cancer:http://youtube.com/watch?v=5jqQxuVncmc
Outline:Part 1 - The Fight Against Cancer
I. Cancer: Barriers to therapeuticsII. Cancer: Current Diagnostics & TherapeuticsIII. Definition of Nanotechnology
A. What it is isB. How it is made
V. Examples of early Nanotechnology
Part 2 - DNA as new NanotechnologyVI. Properties of DNAVII. Innovative uses of DNA-folding Pathways VIII. DiagnosticsIX. Drug releaseX. The Shape of Things to Come
DNA Nanotechnology: PropertiesVersatile: Information on multiple levels
Nucleic acid sequence
2° & 3 ° Structure
State Dependent: f(x):Energy Environment
H = E + PV
Designed DNA molecules: Principles and Applications of Nanotechnology
Condon, Anne Nature Reviews (2006) 7: 565-575
Designed DNA molecules: Principles and Applications of Nanotechnology
Condon, Anne Nature Reviews (2006) 7: 565-575
An Autonomous Molecular Computer for Logical Control of Gene Expression
Yaakov Benenson, Binyamin Gil, Uri Ben-Dor, Rivka Adar & Ehud Shapiro Nature (2004) 429: 423-429Prostate Cancer:
PPAP2BLipid phosphate phosphohydrolase (Vascular endothelial growth factor and type I collagen inducible protein) (VCIP)
GSTP1Glutathione S-transferase. Role in detoxification by catalyzing the conjugation of many hydrophobic and electrophilic compounds with reduced glutathione.
PIM1ATP-dependent Lon protease, involved in degradation of misfolded proteins in mitochondria; required for biogenesis and maintenance of mitochondria
HPNHepsin, a Putative Cell-Surface Serine Protease, is Required for Mammalian Cell Growth
DNA-folding Pathways and their uses continued…
The Shape of Things to come
Prospective Health*:Prevention:•Earlier detection•Gene expression data•Remission prevention
Treatment:•Greater specificity•Real-time confirmation•Diagnostic and action taking abilities•Reprogramming
Next Generation Gene Therapy:
IL-2 MHC-I/IIBool statement IFN- IFN- IFN- Constitutive Promotor Viral/Bacterial Ag
Bool statement Constitutive Promotor Apoptosis Array
Immune System Mobilization coupled with Antigen Presentation:
Self-Destruct Program:
Anti-cyclin ArrayBool statement Constitutive Promotor
Cell Cycle Downregulation (Growth):
Nuclear Reprogramming (Repair):
p53Bool statement Constitutive Promotor Rb Reporter
Reporter
Reporter
Reporter
Multistage Nanodevice
Conclusion: What does this mean?
Diagnostic
Therapeutics
Repertoire of Genetic Engineering
Miniaturization
Artificial NS
References:[1] Condon, Anne. Designed DNA molecules: principles and applications of molecular nanotechnology. Nature Reviews (2006) 7: 565-575.
[2] Ferrari, Mauro. Cancer nanotechnology: oppurtunities and challenges. Nature Reviews (2005) 5: 161-171.
[3] Beneson, Y., Gil, B., Ben-Dor, U., Rivka, A. and Shapiro, E. An autonomous molecular computer for logical control of gene expression. Nature (2004) 429: 423-429.
[4] Beneson, Y., Gil, B., Ben-Dor, U., Rivka, A. and Shapiro, E. An autonomous molecular computer for logical control of gene expression. Nature (2001) 414: 430-434.
[5] Lu, Y., Liu, J. Functionjla DNA nanotechnology: emerging applications of DNAzymes and aptambers. Current Opinion in Biotechnology (2006) 17: 580-588.
[6] Dittmer, W., Reuter, A., Simmel, F. A DNA-based machine that can cyclically bind and release thrombin. Angewandte Chemistry International Edition (2004) 43: 3549-3553.