SS -1 PAC 8/18/11 Recoding the Genome Peter Carr 18 August 2011 FAB7 Lima, Peru.
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Transcript of SS -1 PAC 8/18/11 Recoding the Genome Peter Carr 18 August 2011 FAB7 Lima, Peru.
SS -1PAC 8/18/11
Recoding the Genome
Peter Carr
18 August 2011
FAB7
Lima, Peru
SS -2PAC 8/18/11
DNA On-Demand
103 106105104
rewrite genomesminimal lifegenetic circuits
metabolic pathways
individual genesassembly scaffolds
vaccinesgene therapy
DNA basepairs
SS -3PAC 8/18/11 Carr & Church (2009) Nature Biotech.
1
10
100
1000
10000
100000
1000000
10000000
1950 1960 1970 1980 1990 2000 2010 2020
year
nu
cleo
tid
e b
on
ds
organic chemistry
biochemistry
biology
How big can we go?
SS -4PAC 8/18/11
The basic genetic code
ACGT
4 letters
ACGT
4 letters
X
ACGT
4 letters
X
AAAAACAAGAATACAACCACGACT...
64 words(codons)
=
SS -5PAC 8/18/11
Second Position
SS -6PAC 8/18/11
By engineering new genetic codes we can:
• produce organisms immune to viruses
• make universal systems for “plug and play” with new amino acids
new roomfor plug &
play
• block exchange of genes, a “genetic firewall”
rearrangeto blockfunction
Second Position
SS -7PAC 8/18/11
Multiplex Automated Genome Engineering (MAGE)
“Find and replace” with
the DNA of the genome
SS -8PAC 8/18/11
Key features of MAGE:
• Multiplexed: can address many sites at once
• Targeted: modifies specific sequences; changes made can be specific or random
• Iterated: weak efficiency can be compensated by automating many cycles of modification
• Tunable: can control the range of diversity generated in a population
• Clean: no DNA scars, no resistance gene markers, etc.
SS -9PAC 8/18/11
All 314 sites in the genome modified(across 32 strains)
SS -10PAC 8/18/11
Genome Engineeringbase pairs to megabases
SS -11PAC 8/18/11
Joseph Jacobson • Bram Sterling* • Chris Emig • Sam Hwang
George Church (HMS)• Farren Isaacs• Harris Wang• Marc LaJoie
Shuguang Zhang (MIT)
Funding: NSF
Thanks to:
SS -12PAC 8/18/11
Atoms to bits...to atoms to bits
receivertransmitter
Box 1 Box 2me
you
it
clinical + research
data
genetic counseling
health statistics
forensics
basic research
molecules
experiments
G A T T A C A
SS -13PAC 8/18/11
Personal
Box 1
MY GENES
Box 2
How will drugs X, Y, Z
affect ME?
MY TREATMENT
How will MY BODY metabolize drugs X, Y, Z?
SS -14PAC 8/18/11
Box 1
NEW PATHOGEN
Box 2
Analyze the PARTS
RAPID RESPONSE
Test existing DRUGS at many sites
Preliminary VACCINE
Community
SS -15PAC 8/18/11
MY IDEA
Box 2
new biochemistry
MY DESIGN FOR...
DNA nanostructures
new vaccines
novel organisms
Creativity