Multi-Input RNAi-Based Logic Circuit for Identification of Specific Cancer Cells

Abstract

Engineered biological systems that integrate multi-input sensing, sophisticated information processing, and precisely regulated actuation in living cells could be useful in a variety of applications. For example, anticancer therapies could be engineered to detect and respond to complex cellular conditions in individual cells with high specificity. Here, we show a scalable transcriptional/posttranscriptional synthetic regulatory circuit--a cell-type "classifier"--that senses expression levels of a customizable set of endogenous microRNAs and triggers a cellular response only if the expression levels match a predetermined profile of interest. We demonstrate that a HeLa cancer cell classifier selectively identifies HeLa cells and triggers apoptosis without affecting non-HeLa cell types. This approach also provides a general platform for programmed responses to other complex cell states.

Implementation of a genetic logic circuit: bio-register

“…Both of the development in molecular biology and engineering can be applied in. Many scholars have been using the past welldeveloped ideas to explore biomolecular computing (Wang and Buck 2012;Miyamoto et al 2013;Xie et al 2011) in recent years. Logic circuits in synthetic biology are one of the research interests in systems biology (Gardner et al 2000;Anderson et al 2007;Siuti et al 2013;Moon et al 2012), which are extremely similar to electronic circuits in electronics.…”

Genetic programs can be compressed and autonomously decompressed in live cells

“…Here we support this hypothesis by describing an experimental procedure for compressing a genetic program and its subsequent autonomous decompression and execution in human cells. As a test-bed we choose an RNAi cell classifier circuit 25 that comprises redundant DNA sequence and is therefore amenable for compression, as are many other complex gene circuits 15, 18, 26–28 . In one example, we implement a compressed encoding of a ten-gene four-input AND gate circuit using only four genetic constructs.…”

“…The RNAi classifier 25 comprises multiple sensor modules that relay the concentration of their cognate miRNA inputs to the computing module, which further integrates the information into a single readout (Fig. 1a).…”

“…Initially, we considered a two-input miRNA classifier implementing the logic AND gate “miR-21 AND miR-146a”. A variant of this circuit based on a published approach 25 , called the “source” circuit, contains five genes. We developed a compression process to eliminate sequence redundancy, as follows.…”

A supramolecular keypad lock

“…[1][2][3] The challenge of achieving the design of molecules that are capable of a predetermined logic operation has received important backup from smart applications of molecular logic gates in sensing, drug delivery, theranostics, and materials chemistry. [4][5][6][7][8][9][10] Among the different logic operations, those that imply a memory function belong to the most demanding ones in terms of their chemical design. 11 This type of logic, known as sequential logic, results in differentiated outputs depending on the input history of the device.…”