期刊
NUCLEIC ACIDS RESEARCH
卷 38, 期 8, 页码 2692-2701出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkq117
关键词
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资金
- Bauer Fellows program
- National Institute of General Medical Sciences (NIIGMS) [GM068763-01, GM068763]
- Harvard College Research Program (HCRP)
- Harvard's Program for Research in Science and Engineering (PRISE)
- National Institute of General Medical Sciences Center
- Direct For Biological Sciences
- Div Of Molecular and Cellular Bioscience [1032343] Funding Source: National Science Foundation
Synthetic in vivo molecular 'computers' could rewire biological processes by establishing programmable, non-native pathways between molecular signals and biological responses. Multiple molecular computer prototypes have been shown to work in simple buffered solutions. Many of those prototypes were made of DNA strands and performed computations using cycles of annealing-digestion or strand displacement. We have previously introduced RNA interference (RNAi)-based computing as a way of implementing complex molecular logic in vivo. Because it also relies on nucleic acids for its operation, RNAi computing could benefit from the tools developed for DNA systems. However, these tools must be harnessed to produce bioactive components and be adapted for harsh operating environments that reflect in vivo conditions. In a step toward this goal, we report the construction and implementation of biosensors that 'transduce' mRNA levels into bioactive, small interfering RNA molecules via RNA strand exchange in a cell-free Drosophila embryo lysate, a step beyond simple buffered environments. We further integrate the sensors with our RNAi 'computational' module to evaluate two-input logic functions on mRNA concentrations. Our results show how RNA strand exchange can expand the utility of RNAi computing and point toward the possibility of using strand exchange in a native biological setting.
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