advancing nano-biotechnologysites.nationalacademies.org/cs/groups/pgasite/documents/webpage/… ·...
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Advancing Nano-Biotechnology
Jonathan S. Dordick, Ph.D.
Rensselaer Polytechnic Institute
Troy, NY 12180 USA
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New York’s Nanotechnology Model at Work in Biotechnology
• Tremendous leveraging of NIH, NSF, DOE, and DOD
funding
• Opportunities for upstate engineering and downstate
biomedical research collaborations
• Entry of “big data” into the nano-biotechnology research
space
• Innovation occurs by exploring new ways to use
biotechnology and leading to new products, processes,
and businesses
• NY State has a unique opportunity to extend its “nanotech
model” to biotechnology, and engage more the federal
government and a broader range of industries
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Contrasting Nanotechnology and Biotechnology
3
Nanotechnology Biotechnology
Pre-2010
Post-2010
Advantages:
• Processing/Manufacturing
• Man-made
• Collaboratively established
Disadvantages:
• Difficult to control < 50 nm
• Limited compatibility with
biological systems
• Not environmentally benign
Advantages:
• Exquisite selectivity in shape,
size, biochemistry
• Nature “invested” billions of
years to develop
• Environmentally benign and
biocompatible
Disadvantages:
• Nature is smarter than us
• Isolationism with little
collaboration
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Bioactive
Products ???
Structures
&
Architectures
Unique Functions
Nature: The Ultimate Nanotechnologist
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Fundamental
Knowledge
Gaps
Nanotechnology Enables us to Break Away from Nature’s Boundaries
Processing &
Manufacturing
NANOMATERIALS
BIOMOLECULES
POLYMER
S
Support through NSF and the NSEC Program
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Opening Up New Opportunities: Collaborations are Required
Biomedicine Pathogen
Decontamination
Drug
Discovery
Affordable Healthcare
Technologies radio waves
Ca2+
outside the cell
cytoplasm
iron nanoparticle
Calcineurin
NFATc
PPP
SRE CRE NFAT RE Bioengineered insulin NFATn
nucleus
TRPV1His, NF Ins, PBSTRPV1His, NF Ins, 1st NP Treatment
TRPV1His, NF Ins, 2nd NP Treatment
MRSA
100 nM Ketoconazole
250 nM Sulfaphenazole
100 nM Ketoconazole
250 nM Sulfaphenazole
10 nM Quinidine
100 nM Ketoconazole
250 nM Sulfaphenazole
10 nM Quinidine
CYP3A4
CYP2D6
CYP2C9
CY
P3A
4 A
cti
vit
y (
% o
f C
on
tro
l)
0
20
40
60
80
100
120
140 Data on chip , in alginateData from 384-well plate, in solution
Ketoconazole(100 nM)
Sulfaphenazole (250 nM)
Quinidine (10 nM)
CY
P2
C9 A
cti
vit
y (
% o
f C
on
tro
l)
0
20
40
60
80
100
120
140 Data on chip, in alginateData from 384-well plate, in solution
Ketoconazole(100 nM)
Sulfaphenazole (250 nM)
Quinidine(10 nM)
CY
P2
D6
Ac
tiv
ity
(%
of
Co
ntr
ol)
0
20
40
60
80
100
120
140 Data on chip , in alginateData from 384-well plate, in solution
Ketoconazole(100 nM)
Sulfaphenazole (250 nM)
Quinidine (10 nM)
10 nM Quinidine
100 nM Ketoconazole
250 nM Sulfaphenazole
100 nM Ketoconazole
250 nM Sulfaphenazole
10 nM Quinidine
100 nM Ketoconazole
250 nM Sulfaphenazole
10 nM Quinidine
CYP3A4
CYP2D6
CYP2C9
CY
P3A
4 A
cti
vit
y (
% o
f C
on
tro
l)
0
20
40
60
80
100
120
140 Data on chip , in alginateData from 384-well plate, in solution
Ketoconazole(100 nM)
Sulfaphenazole (250 nM)
Quinidine (10 nM)
CY
P2
C9 A
cti
vit
y (
% o
f C
on
tro
l)
0
20
40
60
80
100
120
140 Data on chip, in alginateData from 384-well plate, in solution
Ketoconazole(100 nM)
Sulfaphenazole (250 nM)
Quinidine(10 nM)
CY
P2
D6
Ac
tiv
ity
(%
of
Co
ntr
ol)
0
20
40
60
80
100
120
140 Data on chip , in alginateData from 384-well plate, in solution
Ketoconazole(100 nM)
Sulfaphenazole (250 nM)
Quinidine (10 nM)
10 nM Quinidine
thesignaltonoise.com
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Societal Drivers for Bioengineered Safe Environments
• Community infrastructure susceptible to
antibiotic-resistant microorganisms
Hospital-acquired infections are the 4th/5th leading
cause of preventable death in the U.S.
WHO we are headed back to the early 20th
Century where many infections were lethal
Routine surgeries may go undone
Antibiotic use in food industry is literally killing us
• Nearly 50 million cases of food poisoning
annually in the U.S. alone.
Economic impact of $7B annually and 1/4 of all
freshwater use
Annual energy waste equivalent to ca. one month of
petroleum use
• Lack of clean water devastates society
Developing world
Developed world following natural/man-made
disasters
Safe Food Processing
and Packaging
Source: Infectious Diseases Society of America (ISDA)
Boucher et al., Clin. Infect. Dis., 2009
Declining Antibacterial Approvals
Safe and
Sustainable
Healthcare
Infrastructure
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Antistaphylococcal Paints: From Hospitals to Mars
• Highly effective against all MRSA
strains tested
• >99% bactericidal activity in 2 h
Effectiveness against methicillin-
resistant S. aureus (MRSA)
J.S. Dordick, R.S. Kane, C. Collins, D. Metzger, R. Pangule
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“Doctors pour drugs of which they know little,
to cure diseases of which they know less, into
human beings of whom they know nothing.”
Voltaire
(1694-1778)
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Drug Discovery: More Knowledge, Yet More Failure
• Total small
molecule
approvals = 58
in 2009-2011
• Cost for drug
approval now
close to $2
billion
• Patents
covering > $50
billion in
blockbuster
drug revenue
expired in 2010
Innovation
Barrier
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Biology is Complex
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Drug Discovery and Toxicology Screening
Metabolizing enzyme
toxicology assay Chip
Rapid and Early Removal of Bad Drugs
Before Going to Clinical Trials
DataChip
Combined
Chips
MetaChip
Data analysis
toxicology assay Chip
Human/rat
enzymes
Target
cells
Your Liver’s Function Your Body
RPI, UC Berkeley, and Solidus
Biosciences, Inc. (begun in NY)
Support by NIH, Pharma,
Cosmetic, Chemical Co’s
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Interface of Nano-Bio-Big Data for Effective and Affordable Healthcare
thesignaltonoise.com digitalreasoning.com
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The Emerging Opportunity: Interface of Nano-Bio-Big Data for Effective and Affordable Healthcare
Research &
Development
Clinical/Translational Healthcare Infrastructure
Therapeutics and
Diagnostics Discovery
Whole Body “Sensors” Networks of Sensors
Biochips &
Miniaturization
Personalized Clinical Trials Big Data
“Omics” Big Data Patient Treatment Regimens
Analytical
Methodologies
Reduced Delivery Costs
• Payers
• Hospitals
• Patients
• Government
Big Data
• NY State can leverage its investment in microelectronics to build the “new”
biotechnology
• The expertise exists in biotechnology, nanotechnology, biomedical research, and
emerging big data
• Investment must include support to bring VC investors to NY and foster pre-
competitive investments
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On-Demand Pharmaceuticals: Tailoring Drugs to YOUR Genetic Makeup
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NY State Has Fostered the Nano-Bio Infrastructure at Rensselaer
Center for Biotechnology
& Interdisciplinary Studies
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Biomolecule-Nanomaterial Formulations in Biomedical Therapies
Transient Receptor Potential Channel V1capsaicin receptor
vanilloid receptor 1 radio waves
Ca2+
outside the cell
cytoplasm
iron nanoparticle
Calcineurin
NFATc
PPP
SRE CRE NFAT RE Bioengineered insulin NFATn
nucleus
TRPV1His, NF Ins, PBSTRPV1His, NF Ins, 1st NP Treatment
TRPV1His, NF Ins, 2nd NP Treatment
Stanley et al. Science 336, 604 (2012).
• Using nanotechnology and microelectronics to achieve therapeutic
outcomes
• Possible impact in neurodegenerative diseases (e.g., Alzheimer’s,
Parkinson’s, etc.), diabetes, others
• Could not have been achieved without collaborative, multidisciplinary
science, engineering, and medicine (collaboration with Dr. Jeffrey
Friedman, Rockefeller University)
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Opportunities at the Nano-Bio Interface in Advancing Drug Discovery
• Mimicking the human body requires cell-based and protein-based materials
• These materials are effective due to nanoscale matrix components that
provide optimum environments for biological activity
• Can be applied to rapid drug discovery and toxicity screening, control of stem
cell biology, and regenerative medicine
• Ideally suited to personalized medicine
Drug Toxicity Stem Cells Biotechnology