title: An autonomous molecular computer for logical control of gene expression.
abstract: Early biomolecular computer research focused on laboratory-scale, human-operated computers for complex computational problems. Recently, simple molecular-scale autonomous programmable computers were demonstrated 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; 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 associated with models of small-cell lung cancer and prostate cancer, and to produce a single-stranded DNA molecule modelled after an anticancer drug.
authors.affiliation: Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Yaakov
authors.initials: Y
authors.lastname: Benenson
authors.forename: Binyamin
authors.initials: B
authors.lastname: Gil
authors.forename: Uri
authors.initials: U
authors.lastname: Ben-Dor
authors.forename: Rivka
authors.initials: R
authors.lastname: Adar
authors.forename: Ehud
authors.initials: E
authors.lastname: Shapiro
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D001185:Artificial Intelligence; D001331:Automation / Q000379:methods; D001483:Base Sequence; D015374:Biosensing Techniques / Q000379:methods; D018288:Carcinoma, Small Cell / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D039301:Computers, Molecular; D016373:DNA, Antisense / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D004277:DNA, Single-Stranded / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D015195:Drug Design; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005818:Genetic Engineering; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D008297:Male; D017354:Point Mutation / Q000235:genetics; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012984:Software; D013269:Stochastic Processes
chemical_list: D000970:Antineoplastic Agents; D016373:DNA, Antisense; D004277:DNA, Single-Stranded; D012333:RNA, Messenger