DNA Nanotechnology Dr. Tai-ping Sun Biology 280S: Biotechnology & Genetic Engineering Joshua Mendoza-Elias Fall 2008 In Cancer Therapeutics

Dr. Tai-ping Sun

Biology 280S: Biotechnology & Genetic Engineering

Joshua Mendoza-Elias

Fall 2008

Outline Part 1 - The Fight Against Cancer I. Cancer: Barriers to therapeutics II. Cancer: Current Diagnostics & Therapeutics III. Definition of Nanotechnology A. What it is is B. How it is made V. Examples of early Nanotechnology Part 2 - DNA as new Nanotechnology VI. Properties of DNA VII. Innovative uses of DNA-folding Pathways VIII. Diagnostics IX. Drug release X. The Shape of Things to Come

Part 1 - The Fight Against Cancer

I. Cancer: Barriers to therapeutics

II. Cancer: Current Diagnostics & Therapeutics

III. Definition of Nanotechnology

A. What it is is

B. How it is made

V. Examples of early Nanotechnology

Part 2 - DNA as new Nanotechnology

VI. Properties of DNA

VII. Innovative uses of DNA-folding Pathways

VIII. Diagnostics

IX. Drug release

X. The Shape of Things to Come

Cancer Clinical 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

Clinical 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-antigen B. Clonal Evolution  . Tumour structures  . Cancer is “unique”  . Damage to healthy cells

 . Immune System Surveillance

A. Self-antigen

B. Clonal Evolution

 . Tumour structures

 . Cancer is “unique”

 . Damage to healthy cells

Standing Order: Diagnostics & Therapeutics Diagnostics: Location Histology Stage Treatments: Surgery Chemotherapy Radiotherapy Targeted Therapy Immunotherapy Hormonal Therapy In situ : Breast Cancer tissue 400x

Diagnostics:

Location

Histology

Stage

Treatments:

Surgery

Chemotherapy

Radiotherapy

Targeted Therapy

Immunotherapy

Hormonal Therapy

State of the Art: Cancer Nanotechnology Detection Treatment DNA Microarrays Bio “Finger” Nanoparticles Nanoparticles Earlier detection Better Targeting Imaging Receptor Mediated Lab on Chip Radiation Activated Gene based Metabolic based Tissue Engineering Cells GF scaffolding

Cancer Nanotechnology: Detection Bio “Finger”

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

NCI Alliance for Nanotechnology in Cancer:

http: //youtube .com/watch? v=5jqQxuVncmc

Outline: Part 1 - The Fight Against Cancer I. Cancer: Barriers to therapeutics II. Cancer: Current Diagnostics & Therapeutics III. Definition of Nanotechnology A. What it is is B. How it is made V. Examples of early Nanotechnology Part 2 - DNA as new Nanotechnology VI. Properties of DNA VII. Innovative uses of DNA-folding Pathways VIII. Diagnostics IX. Drug release X. The Shape of Things to Come

Part 1 - The Fight Against Cancer

I. Cancer: Barriers to therapeutics

II. Cancer: Current Diagnostics & Therapeutics

III. Definition of Nanotechnology

A. What it is is

B. How it is made

V. Examples of early Nanotechnology

Part 2 - DNA as new Nanotechnology

VI. Properties of DNA

VII. Innovative uses of DNA-folding Pathways

VIII. Diagnostics

IX. Drug release

X. The Shape of Things to Come

DNA Nanotechnology: Properties Versatile: Information on multiple levels Nucleic acid sequence 2° & 3 ° Structure State Dependent: f(x):  Energy  Environment  H =  E + P  V

Versatile: Information on multiple levels

Nucleic acid sequence

2° & 3 ° Structure

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 : 423-429 Prostate Cancer: PPAP2B Lipid phosphate phosphohydrolase (Vascular endothelial growth factor and type I collagen inducible protein) (VCIP) GSTP1 Glutathione S-transferase. Role in detoxification by catalyzing the conjugation of many hydrophobic and electrophilic compounds with reduced glutathione. PIM1 ATP-dependent Lon protease, involved in degradation of misfolded proteins in mitochondria; required for biogenesis and maintenance of mitochondria HPN Hepsin, a Putative Cell-Surface Serine Protease, is Required for Mammalian Cell Growth

Prostate Cancer:

PPAP2B

Lipid phosphate phosphohydrolase (Vascular endothelial growth factor and type I collagen inducible protein) (VCIP)

GSTP1

Glutathione S-transferase. Role in detoxification by catalyzing the conjugation of many hydrophobic and electrophilic compounds with reduced glutathione.

PIM1

ATP-dependent Lon protease, involved in degradation of misfolded proteins in mitochondria; required for biogenesis and maintenance of mitochondria

HPN

Hepsin, 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

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/II Bool 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 Array Bool statement Constitutive Promotor Cell Cycle Downregulation (Growth): Nuclear Reprogramming (Repair): p53 Bool statement Constitutive Promotor Rb Reporter Reporter Reporter Reporter

Multistage Nanodevice

Conclusion: What does this mean? Diagnostic Therapeutics Repertoire of Genetic Engineering Miniaturization Artificial NS

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.

[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.