Programming DNA-Based Biomolecular Reaction Networks on Cancer Cell Membranes.

DNA is a highly programmable biomolecule and has been used to construct biological circuits for different purposes. An important development of DNA circuits is to process the information on receptors on cell membranes. In this Communication, we introduce an architecture to program localized DNA-based biomolecular reaction networks on cancer cell membranes. Based on our architecture, various types of reaction networks have been experimentally demonstrated, from simple linear cascades to reaction networks of complex structures. These localized DNA-based reaction networks can be used for medical applications such as cancer cell detection. Compared to prior work on DNA circuits for evaluating cell membrane receptors, the DNA circuits made by our architecture have several major advantages including simpler design, lower leak, lower cost, and higher signal-to-background ratio.

Fast and compact DNA logic circuits based on single-stranded gates using strand-displacing polymerase.

DNA is a reliable biomolecule with which to build molecular computation systems. In particular, DNA logic circuits (diffusion-based) have shown good performance regarding scalability and correctness of computation. However, previous architectures of DNA logic circuits have two limitations. First, the speed of computation is slow, often requiring hours to compute a simple function. Second, the circuits are of high complexity regarding the number of DNA strands. Here, we introduce an architecture of DNA logic circuits based on single-stranded logic gates using strand-displacing DNA polymerase. The logic gates consist of only single DNA strands, which largely reduces leakage reactions and signal restoration steps such that the circuits are improved in regard to both speed of computation and the number of DNA strands needed. Large-scale logic circuits can be constructed from the gates by simple cascading strategies. In particular, we have demonstrated a fast and compact logic circuit that computes the square-root function of four-bit input numbers.

Improving the Performance of DNA Strand Displacement Circuits by Shadow Cancellation.

DNA strand displacement circuits are powerful tools that can be rationally engineered to implement molecular computing tasks because they are programmable, cheap, robust, and predictable. A key feature of these circuits is the use of catalytic gates to amplify signal. Catalytic gates tend to leak; that is, they generate output signal even in the absence of intended input. Leaks are harmful to the performance and correct operation of DNA strand displacement circuits. Here, we present "shadow cancellation", a general-purpose technique to mitigate leak in catalytic DNA strand displacement circuits. Shadow cancellation involves constructing a parallel shadow circuit that mimics the primary circuit and has the same leak characteristics. It is situated in the same test tube as the primary circuit and produces "anti-background" DNA strands that cancel "background" DNA strands produced by leak. We demonstrate the feasibility and strength of the shadow leak cancellation approach through a challenging test case, a cross-catalytic feedback DNA amplifier circuit that leaks prodigiously. Shadow cancellation dramatically reduced the leak of this circuit and improved the signal-to-background difference by several fold. Unlike existing techniques, it makes no modifications to the underlying amplifier circuit and is agnostic to its leak mechanism. Shadow cancellation also showed good robustness to concentration errors in multiple scenarios. This work introduces a direction in leak reduction techniques for DNA strand displacement amplifier circuits and can potentially be extended to other molecular amplifiers.

An Odd Parity Checker Prototype Using DNAzyme Finite State Machine.

A finite-state machine (FSM) is an abstract mathematical model of computation used to design both computer programs and sequential logic circuits. Considered as an abstract model of computation, FSM is weak; it has less computational power than some other models of computation such as the Turing machine. This paper discusses the finite-state automata based on Deoxyribonucleic Acid (DNA) and different implementations of DNA FSMs. Moreover, a comparison was made to clarify the advantages and disadvantages of each kind of presented DNA FSMS. Since it is a major goal for nanoscince, nanotechnology and super molecular chemistry is to design synthetic molecular devices that are programmable and run autonomously. Programmable means that the behavior of the device can be modified without redesigning the whole structure. Autonomous means that it runs without externally mediated change to the work cycle. In this paper we present an odd Parity Checker Prototype Using DNAzyme FSM. Our paper makes use of a known design for a DNA nanorobotic device due to Reif and Sahu for executing FSM computations using DNAzymes. The main contribution of our paper is a description of how to program that device to do a FSM computation known as odd parity checking. We describe in detail finite state automaton built on 10-23 DNAzyme, and give its procedure of design and computation. The design procedure has two major phases: designing the language potential alphabet DNA strands, and depending on the first phase to design the DNAzyme possible transitions.