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

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