Journal Article

An autonomous molecular computer for logical control of gene expression

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

2004

Overview

Early biomolecular computer research focused on laboratory-scale, human-operated computers for complex computational problems 1 , 2 , 3 , 4 , 5 , 6 , 7 . Recently, simple molecular-scale autonomous programmable computers were demonstrated 8 , 9 , 10 , 11 , 12 , 13 , 14 , 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 automaton 12 , 13 , 14 , 15 , 16 , 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 genes 18 , 19 , 20 , 21 , 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.

• Publisher: Nature Publishing Group UK,Nature Publishing,Nature Publishing Group
• Subject: Antineoplastic Agents - administration & dosage / Antineoplastic Agents - chemistry / Antineoplastic Agents - pharmacology / Antitumor agents / Artificial Intelligence / Automation - methods / Base Sequence / Biological and medical sciences / Biosensing Techniques - methods / Biotechnology / Cancer / Carcinoma, Small Cell - diagnosis / Carcinoma, Small Cell - drug therapy / Carcinoma, Small Cell - genetics / Computer applications / Computers, Molecular / Deoxyribonucleic acid / DNA / DNA, Antisense - administration & dosage / DNA, Antisense - chemistry / DNA, Antisense - genetics / DNA, Antisense - pharmacology / DNA, Single-Stranded - administration & dosage / DNA, Single-Stranded - chemistry / DNA, Single-Stranded - genetics / DNA, Single-Stranded - pharmacology / Drug Design / Fundamental and applied biological sciences. Psychology / Gene expression / Gene Expression Profiling / Gene Expression Regulation, Neoplastic - drug effects / General aspects / Genetic Engineering / Genetic Therapy - methods / Humanities and Social Sciences / Humans / letter / Lung cancer / Male / Mathematics in biology. Statistical analysis. Models. Metrology. Data processing in biology (general aspects) / Methods. Procedures. Technologies / Molecular biology / mRNA / multidisciplinary / Others / Point Mutation - genetics / Programmable logic controllers / Prostate cancer / Prostatic Neoplasms - diagnosis / Prostatic Neoplasms - drug therapy / Prostatic Neoplasms - genetics / Q1 / Ribonucleic acid / RNA / RNA, Messenger - analysis / RNA, Messenger - genetics / Science / Science (multidisciplinary) / Software / Stochastic Processes / Various methods and equipments