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
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
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)
Regulation of competing transitions
Validation of the diagnostic automata
Demonstration of Drug Administration