X-Message-Number: 24013
Date: Thu, 29 Apr 2004 17:40:59 +1000
From: Simon Carter <>

Subject: An autonomous molecular computer for logical control of gene expression

Nature Advanded Online Publication

Published online 28 April 2004

doi:10.1038/nature02551

An autonomous molecular computer for logical control of gene expression

YAAKOV BENENSON 1,2, BINYAMIN GIL 2, URI BEN-DOR 1, RIVKA ADAR 2 & EHUD SHAPIRO
1,2

1 Department of Computer Science and Applied Mathematics, Weizmann Institute of
Science, Rehovot 76100, Israel

2 Department of Biological Chemistry, Weizmann Institute of Science, Rehovot
76100, Israel

Correspondence and requests for materials should be addressed to E.S.
().


Early biomolecular computer research focused on laboratory-scale, human-operated
computers for complex computational problems1-7. Recently, simple
molecular-scale autonomous programmable computers were demonstrated8-15
allowing both input and output information to be in molecular form. Such
computers, using biological molecules as input data and biologically active
molecules as outputs, could produce a system for 'logical' control of
biological processes. Here we describe an autonomous biomolecular computer
that, at least in vitro, logically analyses the levels of messenger RNA
species, and in response produces a molecule capable of affecting levels of
gene expression. The computer operates at a concentration of close to a
trillion computers per microlitre and consists of three programmable modules: a
computation module, that is, a stochastic molecular automaton12-17; an input
module, by which specific mRNA levels or point mutations regulate software
molecule concentrations, and hence automaton transition probabilities; and an
output module, capable of controlled release of a short single-stranded DNA
molecule. This approach might be applied in vivo to biochemical sensing,
genetic engineering and even medical diagnosis and treatment. As a proof of
principle we programmed the computer to identify and analyse mRNA of
disease-related genes18-22 associated with models of small-cell lung cancer and
prostate cancer, and to produce a single-stranded DNA molecule modelled after
an anticancer drug.

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