Why synthsize genes and genomes? 10 3 10 6 10 5 10 4 -minimal life -genome rewrite -genetic circuits...
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Transcript of Why synthsize genes and genomes? 10 3 10 6 10 5 10 4 -minimal life -genome rewrite -genetic circuits...
![Page 1: Why synthsize genes and genomes? 10 3 10 6 10 5 10 4 -minimal life -genome rewrite -genetic circuits -metabolic pathways -vaccines -gene therapy -individual.](https://reader035.fdocuments.us/reader035/viewer/2022062518/5697bf721a28abf838c7e93b/html5/thumbnails/1.jpg)
Why synthsize genes and genomes?
103 106105104
-minimal life-genome rewrite-genetic circuits
-metabolic pathways
-vaccines-gene therapy-individual genes
-assembly scaffolds
DNA length(base pairs)
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Error Correction with Flawed Components
A C G G
T C T G
A C T A
A C T GWinograd and Cowan (1967) “Reliable Computation in the Presence of Noise”
A circuit containing N (error-free) gates can be simulated
with probability of error at most , using N log(N/) faulty gates, which fail with probability p, so long as p<pth.
von Neumann (1956)
DNA “consensus vote”
![Page 3: Why synthsize genes and genomes? 10 3 10 6 10 5 10 4 -minimal life -genome rewrite -genetic circuits -metabolic pathways -vaccines -gene therapy -individual.](https://reader035.fdocuments.us/reader035/viewer/2022062518/5697bf721a28abf838c7e93b/html5/thumbnails/3.jpg)
x
Mismatch Recognition
+ Nuclease Activity
M
N
x
x
M
N
M
N
M
N
Repair Operation
Complete error correction when no strand is error-free
![Page 4: Why synthsize genes and genomes? 10 3 10 6 10 5 10 4 -minimal life -genome rewrite -genetic circuits -metabolic pathways -vaccines -gene therapy -individual.](https://reader035.fdocuments.us/reader035/viewer/2022062518/5697bf721a28abf838c7e93b/html5/thumbnails/4.jpg)
xM
N
Exchange RepairCopies 1 and 2
Repair Operation
Complete error correction when no strand is error-free
![Page 5: Why synthsize genes and genomes? 10 3 10 6 10 5 10 4 -minimal life -genome rewrite -genetic circuits -metabolic pathways -vaccines -gene therapy -individual.](https://reader035.fdocuments.us/reader035/viewer/2022062518/5697bf721a28abf838c7e93b/html5/thumbnails/5.jpg)
xM
N
Exchange RepairCopies 1 and 2
Repair Operation
Complete error correction when no strand is error-free
![Page 6: Why synthsize genes and genomes? 10 3 10 6 10 5 10 4 -minimal life -genome rewrite -genetic circuits -metabolic pathways -vaccines -gene therapy -individual.](https://reader035.fdocuments.us/reader035/viewer/2022062518/5697bf721a28abf838c7e93b/html5/thumbnails/6.jpg)
Exchange RepairCopies 2 and 3
Repair Operation
Complete error correction when no strand is error-free
![Page 7: Why synthsize genes and genomes? 10 3 10 6 10 5 10 4 -minimal life -genome rewrite -genetic circuits -metabolic pathways -vaccines -gene therapy -individual.](https://reader035.fdocuments.us/reader035/viewer/2022062518/5697bf721a28abf838c7e93b/html5/thumbnails/7.jpg)
Exchange RepairCopies 2 and 3
Current milestone: 1 error per 20,000 bpNext milestone: 1 error per 100,000 bp
Repair Operation
Complete error correction when no strand is error-free
![Page 8: Why synthsize genes and genomes? 10 3 10 6 10 5 10 4 -minimal life -genome rewrite -genetic circuits -metabolic pathways -vaccines -gene therapy -individual.](https://reader035.fdocuments.us/reader035/viewer/2022062518/5697bf721a28abf838c7e93b/html5/thumbnails/8.jpg)
Why Synthetic Genomes?
• Drug biosynthesis of new proteins– Nonnatural Amino Acids
• Optimal codons
• Genome stability Safer Bio-isolation
Nonnatural amino acids Genome Engineering
Cellular ChassisVirus-resistant strains
E. coli rE.coli
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Recoding E.coli: rE.coli
E. ColiMG16554.6 MB
Remove tRNAs, tRNA synthetases- three codons “free”- Viral resistance?
2. AGR (R) > CGR (R)
Remove RF1- one codon available for unnatural amino acids- Viral resistance?
1. UAG stop > UAA stop
1. Codons: AGY Ser > UCX Ser2. tRNAs: AGY Ser > AGY Leu3. Codons: UUR/CUX Leu > AGY Ser4. tRNAs: UUR Leu > UUR Ser5. Codons: UCX Ser > UUR Ser (Leu & Ser now switched)
tRNAs: AGY (S) > AGY (L)
3. AGY (S) > UCX (S)
tRNAs: UUR (L) > UUR (S)
3. UUR/CUX (L) > AGY (S)