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.