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An autonomous molecular computer for logical control of gene expression Yaakov Benenson, Binyamin Gil, Uri Ben-Dor, Rivka Adar & Ehud Shapiro Weizmann Institute of Science, Israel

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Page 1: An autonomous molecular computer for logical control of gene expression Yaakov Benenson, Binyamin Gil, Uri Ben-Dor, Rivka Adar & Ehud Shapiro Weizmann

An autonomous molecular computer for logical control of gene expression

Yaakov Benenson, Binyamin Gil, Uri Ben-Dor, Rivka Adar & Ehud Shapiro

Weizmann Institute of Science, Israel

Page 2: An autonomous molecular computer for logical control of gene expression Yaakov Benenson, Binyamin Gil, Uri Ben-Dor, Rivka Adar & Ehud Shapiro Weizmann

An autonomous biomolecular computer that, logically analyzes the levels of mRNA species, and in response produces a molecule capable of affecting levels of gene expression, which is a drug.

Logical design and modular organization Input - Identification of disease indicators Computation - Diagnosis Output – Drug administration

Page 3: An autonomous molecular computer for logical control of gene expression Yaakov Benenson, Binyamin Gil, Uri Ben-Dor, Rivka Adar & Ehud Shapiro Weizmann

Example diagnostic rules

Small-cell lung cancer If ASCL1↑ & GRIA2↑ & INSM1↑ & PTTG↑ then

Administer TCTCCCAGCGTGCGCCAT (oblimersen-a drug that may kill cancer cells by blocking the production of a protein that makes cancer cells live longer. Also called bcl-2 antisense oligodeoxynucleotide G313

9 and augmerosen) Prostate cancer

If PPAP2B↓ & GSTP1↓ & PIM1↑ & HPN↑ then Administer GTTGGTATTGCACAT(MDM2 antisense strand)

Page 4: An autonomous molecular computer for logical control of gene expression Yaakov Benenson, Binyamin Gil, Uri Ben-Dor, Rivka Adar & Ehud Shapiro Weizmann
Page 5: An autonomous molecular computer for logical control of gene expression Yaakov Benenson, Binyamin Gil, Uri Ben-Dor, Rivka Adar & Ehud Shapiro Weizmann
Page 6: An autonomous molecular computer for logical control of gene expression Yaakov Benenson, Binyamin Gil, Uri Ben-Dor, Rivka Adar & Ehud Shapiro Weizmann
Page 7: An autonomous molecular computer for logical control of gene expression Yaakov Benenson, Binyamin Gil, Uri Ben-Dor, Rivka Adar & Ehud Shapiro Weizmann
Page 8: An autonomous molecular computer for logical control of gene expression Yaakov Benenson, Binyamin Gil, Uri Ben-Dor, Rivka Adar & Ehud Shapiro Weizmann
Page 9: An autonomous molecular computer for logical control of gene expression Yaakov Benenson, Binyamin Gil, Uri Ben-Dor, Rivka Adar & Ehud Shapiro Weizmann
Page 10: An autonomous molecular computer for logical control of gene expression Yaakov Benenson, Binyamin Gil, Uri Ben-Dor, Rivka Adar & Ehud Shapiro Weizmann
Page 11: An autonomous molecular computer for logical control of gene expression Yaakov Benenson, Binyamin Gil, Uri Ben-Dor, Rivka Adar & Ehud Shapiro Weizmann

Regulation of competing transitions

Page 12: An autonomous molecular computer for logical control of gene expression Yaakov Benenson, Binyamin Gil, Uri Ben-Dor, Rivka Adar & Ehud Shapiro Weizmann

Validation of the diagnostic automata

Page 13: An autonomous molecular computer for logical control of gene expression Yaakov Benenson, Binyamin Gil, Uri Ben-Dor, Rivka Adar & Ehud Shapiro Weizmann

Demonstration of Drug Administration