synthetic biology - stem art munnelly presentation.pdf · synthetic biology: a perspective on its...
TRANSCRIPT
![Page 1: Synthetic Biology - stem art Munnelly Presentation.pdf · Synthetic Biology: A Perspective On Its Potential ... 20+ years in pharmaceuticals, life science tools and molecular diagnostics](https://reader030.vdocuments.site/reader030/viewer/2022040903/5e75b022bbec74000a669ca9/html5/thumbnails/1.jpg)
Genes Pathways Genomes
Kevin Munnelly, President and CEO, Gen9Stem Cells & Regenerative Medicine CongressSeptember 15, 2014
Synthetic Biology:A Perspective On Its Potential In Regenerative Medicine
![Page 2: Synthetic Biology - stem art Munnelly Presentation.pdf · Synthetic Biology: A Perspective On Its Potential ... 20+ years in pharmaceuticals, life science tools and molecular diagnostics](https://reader030.vdocuments.site/reader030/viewer/2022040903/5e75b022bbec74000a669ca9/html5/thumbnails/2.jpg)
Shameless Self Promotion
Gen9 Confidential2
20+ years in pharmaceuticals, life science tools and molecular diagnostics
Board Member
Fast, accurate, inexpensive gene sequencing using molecular motion
Providing functional water soluble variants of any GPCR or
membrane protein
![Page 3: Synthetic Biology - stem art Munnelly Presentation.pdf · Synthetic Biology: A Perspective On Its Potential ... 20+ years in pharmaceuticals, life science tools and molecular diagnostics](https://reader030.vdocuments.site/reader030/viewer/2022040903/5e75b022bbec74000a669ca9/html5/thumbnails/3.jpg)
Gen9 – Synthesizing the Future
3
DrewEndy
Stanford
Bio-engineering
George Church
Harvard
Genetics
Joe Jacobson
MIT
Fabrication
Founded 200935 EmployeesLocated in Cambridge, MA, USA
Founders Investors
![Page 4: Synthetic Biology - stem art Munnelly Presentation.pdf · Synthetic Biology: A Perspective On Its Potential ... 20+ years in pharmaceuticals, life science tools and molecular diagnostics](https://reader030.vdocuments.site/reader030/viewer/2022040903/5e75b022bbec74000a669ca9/html5/thumbnails/4.jpg)
What is Synthetic Biology?
4
"Synthetic biology is:a) the design and
construction of new biological parts, devices and systems and; b) the re-design of existing natural biological systems for useful purposes."
![Page 5: Synthetic Biology - stem art Munnelly Presentation.pdf · Synthetic Biology: A Perspective On Its Potential ... 20+ years in pharmaceuticals, life science tools and molecular diagnostics](https://reader030.vdocuments.site/reader030/viewer/2022040903/5e75b022bbec74000a669ca9/html5/thumbnails/5.jpg)
Synthetic Biology is Creating Future Factories…
…for the Production of Pharmaceuticals, Biofuels and Chemicals
5
to Create Cellular Factories … to Make High Value ProductsUsing Synthetic Genes…
ChemicalsBio-Fuels EnzymesPharmaceuticals
![Page 6: Synthetic Biology - stem art Munnelly Presentation.pdf · Synthetic Biology: A Perspective On Its Potential ... 20+ years in pharmaceuticals, life science tools and molecular diagnostics](https://reader030.vdocuments.site/reader030/viewer/2022040903/5e75b022bbec74000a669ca9/html5/thumbnails/6.jpg)
Products of Synthetic Biology
Gen9 Confidential6
![Page 7: Synthetic Biology - stem art Munnelly Presentation.pdf · Synthetic Biology: A Perspective On Its Potential ... 20+ years in pharmaceuticals, life science tools and molecular diagnostics](https://reader030.vdocuments.site/reader030/viewer/2022040903/5e75b022bbec74000a669ca9/html5/thumbnails/7.jpg)
7
Systems Biology• Construction and analysis of
synthetic regulatory networks• Sophisticated Perturbations
Bimolecular synthesis and fabrication• Optimized drug synthesis• Molecular-scale device fabrication
Biomedical• Artificial immune systems• Cancer and other disease therapies• Tissue generation and regulation• Biosensing• Diagnostics
Synthetic Biology in Medicine
![Page 8: Synthetic Biology - stem art Munnelly Presentation.pdf · Synthetic Biology: A Perspective On Its Potential ... 20+ years in pharmaceuticals, life science tools and molecular diagnostics](https://reader030.vdocuments.site/reader030/viewer/2022040903/5e75b022bbec74000a669ca9/html5/thumbnails/8.jpg)
The Progress of Synthetic Biology
8
De novo Mycoplasma Genome synthesized
S. cerevisiae Chromosome synthesized
DNA
Prokaryote
Eukaryote
Tissue/Organ
Metazoan
Bi-stable Switch in E. coli
Designed Proteins
Synthetic CircuitsParts Libraries BioBricks repository established
2000
2005
2010
2015
2020
1995
![Page 9: Synthetic Biology - stem art Munnelly Presentation.pdf · Synthetic Biology: A Perspective On Its Potential ... 20+ years in pharmaceuticals, life science tools and molecular diagnostics](https://reader030.vdocuments.site/reader030/viewer/2022040903/5e75b022bbec74000a669ca9/html5/thumbnails/9.jpg)
What is Holding Us Back?
9
![Page 10: Synthetic Biology - stem art Munnelly Presentation.pdf · Synthetic Biology: A Perspective On Its Potential ... 20+ years in pharmaceuticals, life science tools and molecular diagnostics](https://reader030.vdocuments.site/reader030/viewer/2022040903/5e75b022bbec74000a669ca9/html5/thumbnails/10.jpg)
Capacity in Base Pairs Per Year
3 Trillion bpAnnual
SequencingCapacity
300 Million bpAnnual
SynthesisCapacity
10,000X Discrepancy
The Opportunity: Reading vs. Writing DNA
![Page 11: Synthetic Biology - stem art Munnelly Presentation.pdf · Synthetic Biology: A Perspective On Its Potential ... 20+ years in pharmaceuticals, life science tools and molecular diagnostics](https://reader030.vdocuments.site/reader030/viewer/2022040903/5e75b022bbec74000a669ca9/html5/thumbnails/11.jpg)
Gene Synthesis: A new Demonstration of Moore’s Law
Disruptive Technologies
Integrated Circuit
Gen9 BioFab®
Simple Circuit Complex Circuit
Oligo Synthesis Gene Synthesis
![Page 12: Synthetic Biology - stem art Munnelly Presentation.pdf · Synthetic Biology: A Perspective On Its Potential ... 20+ years in pharmaceuticals, life science tools and molecular diagnostics](https://reader030.vdocuments.site/reader030/viewer/2022040903/5e75b022bbec74000a669ca9/html5/thumbnails/12.jpg)
Gene Synthesis Ecosystem
Gen9 Confidential12
Parts Library CAD
Bio-Informatics
BioFab®
![Page 13: Synthetic Biology - stem art Munnelly Presentation.pdf · Synthetic Biology: A Perspective On Its Potential ... 20+ years in pharmaceuticals, life science tools and molecular diagnostics](https://reader030.vdocuments.site/reader030/viewer/2022040903/5e75b022bbec74000a669ca9/html5/thumbnails/13.jpg)
On-Demand DNA Applications
13
base
pairs 102 107105104103 106
single genes*
genetic circuits
Pathwaysgenome rewrite
minimal life
![Page 14: Synthetic Biology - stem art Munnelly Presentation.pdf · Synthetic Biology: A Perspective On Its Potential ... 20+ years in pharmaceuticals, life science tools and molecular diagnostics](https://reader030.vdocuments.site/reader030/viewer/2022040903/5e75b022bbec74000a669ca9/html5/thumbnails/14.jpg)
The Promise of Synthetic Biology
14
![Page 15: Synthetic Biology - stem art Munnelly Presentation.pdf · Synthetic Biology: A Perspective On Its Potential ... 20+ years in pharmaceuticals, life science tools and molecular diagnostics](https://reader030.vdocuments.site/reader030/viewer/2022040903/5e75b022bbec74000a669ca9/html5/thumbnails/15.jpg)
Editing Genomes
15
Advancements in technologies for precision editing
Guide RNACas9
Genomic DNA
Repair
Targeted Genome Editing
Synthetic Donor DNA
![Page 16: Synthetic Biology - stem art Munnelly Presentation.pdf · Synthetic Biology: A Perspective On Its Potential ... 20+ years in pharmaceuticals, life science tools and molecular diagnostics](https://reader030.vdocuments.site/reader030/viewer/2022040903/5e75b022bbec74000a669ca9/html5/thumbnails/16.jpg)
Creation of Pluripotent Cells
16
Reprogramming:ERG, KLF4, SOX4, MYB, RORA,
HLF, HOXA5, HOXA9, and HOXA10
iPSFibroblast iPS Cells
Growth
Reprogramming:ERG, KLF4, SOX4, MYB, RORA,
HLF, HOXA5, HOXA9, and HOXA10
PLUS ADDITIONAL Factors
iPS+?Fibroblast
Growth
Pluripotent Reprogramming
![Page 17: Synthetic Biology - stem art Munnelly Presentation.pdf · Synthetic Biology: A Perspective On Its Potential ... 20+ years in pharmaceuticals, life science tools and molecular diagnostics](https://reader030.vdocuments.site/reader030/viewer/2022040903/5e75b022bbec74000a669ca9/html5/thumbnails/17.jpg)
Better Options for Therapy
17
And Disease Treatment
Healthy DonorPatient
Engineered for:• Immune resistance?• Viral Resistance?• Additional disease
fighting capabilities
Engineered for:• Viral Resistance?• Additional disease
fighting capabilities• Anti Aging?
Recipient Patient
![Page 18: Synthetic Biology - stem art Munnelly Presentation.pdf · Synthetic Biology: A Perspective On Its Potential ... 20+ years in pharmaceuticals, life science tools and molecular diagnostics](https://reader030.vdocuments.site/reader030/viewer/2022040903/5e75b022bbec74000a669ca9/html5/thumbnails/18.jpg)
New Therapeutic Companies in Editing Space
18
![Page 19: Synthetic Biology - stem art Munnelly Presentation.pdf · Synthetic Biology: A Perspective On Its Potential ... 20+ years in pharmaceuticals, life science tools and molecular diagnostics](https://reader030.vdocuments.site/reader030/viewer/2022040903/5e75b022bbec74000a669ca9/html5/thumbnails/19.jpg)
Need for Organs
19
Each day, an average of 18 people die waiting for transplants due to organ shortage (>6500 year)
Data from optn.transplant.hrsa.gov and OPTN/SRTR Annual Report.** Data include deceased and living donors
![Page 20: Synthetic Biology - stem art Munnelly Presentation.pdf · Synthetic Biology: A Perspective On Its Potential ... 20+ years in pharmaceuticals, life science tools and molecular diagnostics](https://reader030.vdocuments.site/reader030/viewer/2022040903/5e75b022bbec74000a669ca9/html5/thumbnails/20.jpg)
Humanized Pigs?
20
![Page 21: Synthetic Biology - stem art Munnelly Presentation.pdf · Synthetic Biology: A Perspective On Its Potential ... 20+ years in pharmaceuticals, life science tools and molecular diagnostics](https://reader030.vdocuments.site/reader030/viewer/2022040903/5e75b022bbec74000a669ca9/html5/thumbnails/21.jpg)
Immune Resistant Model Organisms
21
![Page 22: Synthetic Biology - stem art Munnelly Presentation.pdf · Synthetic Biology: A Perspective On Its Potential ... 20+ years in pharmaceuticals, life science tools and molecular diagnostics](https://reader030.vdocuments.site/reader030/viewer/2022040903/5e75b022bbec74000a669ca9/html5/thumbnails/22.jpg)
Iterative genome editing approach to synthesize human compatible organs from animals
Target-cell isolation
Rapid toolbuilding
Accurateassessment
Targetingvalidation
Organ level functional
assays
Editing
Cas9
gRNA
Genome-wide gene discovery
Pig cloning and organ testing
Multipliable genome
engineering
Iterativehumanization of pig organs
DNA synthesis
CRISPR library
Engineered cell library
![Page 23: Synthetic Biology - stem art Munnelly Presentation.pdf · Synthetic Biology: A Perspective On Its Potential ... 20+ years in pharmaceuticals, life science tools and molecular diagnostics](https://reader030.vdocuments.site/reader030/viewer/2022040903/5e75b022bbec74000a669ca9/html5/thumbnails/23.jpg)
Can We Create Large Scale Functional Tissues?
23
![Page 24: Synthetic Biology - stem art Munnelly Presentation.pdf · Synthetic Biology: A Perspective On Its Potential ... 20+ years in pharmaceuticals, life science tools and molecular diagnostics](https://reader030.vdocuments.site/reader030/viewer/2022040903/5e75b022bbec74000a669ca9/html5/thumbnails/24.jpg)
Defining, Writing and Manipulating Genetic Programs
24
A Self-Timed Genetic Program for β cell Differentiation
From the Weiss lab (MIT Synthetic Biology Dept)
![Page 25: Synthetic Biology - stem art Munnelly Presentation.pdf · Synthetic Biology: A Perspective On Its Potential ... 20+ years in pharmaceuticals, life science tools and molecular diagnostics](https://reader030.vdocuments.site/reader030/viewer/2022040903/5e75b022bbec74000a669ca9/html5/thumbnails/25.jpg)
A Sampling of Cell Fate Regulators
25
Targets for Synthetic Biology Reprogramming
J. Fujikura, et al., Genes and Development, Vol. 16,pp. 784‐789, 2002.R. Davis, H. Weintraub, A. B. Lassar, Cell Vol. 51, pp. 987‐1000, 1987.H. Niwa, et. al, Cell, Vol. 123(5), pp. 917‐929, 2005.Ericson, et al., Cell, Vol. 90, pp. 169‐180, 1997.G. Gu, et al., Development Vol. 129, pp. 2447‐2457, 2002.J. Wang, et al., Developmental Biology, Vol. 266, pp. 178‐189, 2004.N. Lavon, et al., Stem Cells, Vol. 24, pp. 1923‐1930, 2006.J. Heit, S. Karnik, S. Kim, Ann. Rev. Cell Dev. Biol. 22: 311‐338, 2006.D. Sinner, et al., Development, Vol. 131, pp. 3069‐3080, 2004J. Briscoe, et al., Nature, Vol. 398, p.622‐627, 1999.T. Jessell, Nature Reviews Genetics, Vol. 1, pp. 21‐29, 2000.M. McCormick, et al., Mol. and Cell. Bio., Vol. 16(10),pp. 5792‐5800, 1996M. Yasunaga, et al., Nature Biotech, Vol. 23(12), 1542‐1550, 2005.C. Vernochet, et al., FEBS Letters, Vol, 510, pp. 94‐98, 2002.
• Gata4, Gata6, Sox17
Endoderm
• MyoD
Muscle
• Cdx2
Trophectoderm
• Ngn3, Pax4, Nkx2.2, Pdx1
Pancreas
• Pparγ
Adipocytes
• Nkx2.2, Nkx6.1, Pax6, Ngn1
Neuronal
![Page 26: Synthetic Biology - stem art Munnelly Presentation.pdf · Synthetic Biology: A Perspective On Its Potential ... 20+ years in pharmaceuticals, life science tools and molecular diagnostics](https://reader030.vdocuments.site/reader030/viewer/2022040903/5e75b022bbec74000a669ca9/html5/thumbnails/26.jpg)
Path to Organ (re)Generation
26
Reprogramming
![Page 27: Synthetic Biology - stem art Munnelly Presentation.pdf · Synthetic Biology: A Perspective On Its Potential ... 20+ years in pharmaceuticals, life science tools and molecular diagnostics](https://reader030.vdocuments.site/reader030/viewer/2022040903/5e75b022bbec74000a669ca9/html5/thumbnails/27.jpg)
Printed Organs
27
![Page 28: Synthetic Biology - stem art Munnelly Presentation.pdf · Synthetic Biology: A Perspective On Its Potential ... 20+ years in pharmaceuticals, life science tools and molecular diagnostics](https://reader030.vdocuments.site/reader030/viewer/2022040903/5e75b022bbec74000a669ca9/html5/thumbnails/28.jpg)
Development Timeline for 3D Tissues/Organs
28
Murphy and Atala. Nature Biotechnology Vol 32, No. 8 (2014)
![Page 29: Synthetic Biology - stem art Munnelly Presentation.pdf · Synthetic Biology: A Perspective On Its Potential ... 20+ years in pharmaceuticals, life science tools and molecular diagnostics](https://reader030.vdocuments.site/reader030/viewer/2022040903/5e75b022bbec74000a669ca9/html5/thumbnails/29.jpg)
Looking Ahead
• Advancement of developmental biology research
• iPS reprogramming
– Therapies
– Tissues
• Applications of amphibian based genetics?
• Generic and personalized model organisms
• SynBio + 3D printing
• Nuclei editing in Brain and neurons
• Anti Aging?
Gen9 Confidential29
Potential to unlock many of life’s mysteries!
![Page 30: Synthetic Biology - stem art Munnelly Presentation.pdf · Synthetic Biology: A Perspective On Its Potential ... 20+ years in pharmaceuticals, life science tools and molecular diagnostics](https://reader030.vdocuments.site/reader030/viewer/2022040903/5e75b022bbec74000a669ca9/html5/thumbnails/30.jpg)
30
InnovationCollaboration
Dedication Inte
gri
tySequence-perfectNext-generation
syn
the
size
d
Gen9process
clo
na
lv
ect
or
lib
rari
es
Ge
ne
Bit
pe
rfe
ct
Ge
ne
Custom
designUSA
genesbase pairs
constructs
pro
du
cts
seq
ue
nce
GeneByte
DNA
dsD
NA
Variant
BioFab
ord
er
synthesis
service
plu
s