1. 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

2. 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

3. 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 G3139 and augmerosen ) Prostate cancer If PPAP2B↓ & GSTP1↓ & PIM1↑ & HPN↑ then Administer GTTGGTATTGCACAT(MDM2 antisense strand)

11. Regulation of competing transitions

12. Validation of the diagnostic automata

13. Demonstration of Drug Administration