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Towards in vivo molecular automata

Dr. Yaakov Benenson,
Harvard University


Molecular automata that combine sensing, computation and actuation (end-to-end automata) enable programmable manipulation of biological systems. A few years ago we constructed a DNA-based test-tube prototype of these systems (1). Recently we have used RNA interference in human cell culture to construct an in vivo 'molecular computer' that implements Boolean logic. In particular, we suggested design guidelines that can in principle be scaled to make arbitrarily complex logic decisions based on endogenous molecular inputs (2). I will discuss these published results and present recent data demonstrating end-to-end automata in in vitro cell-free systems and mammalian cells.

1. Benenson, Y., Gil, B., Ben-Dor, U., Adar, R. & Shapiro, E:
An autonomous molecular computer for logical control of gene expression.
Nature 429, 423-429 (2004).

2. Rinaudo, K., Bleris, L., Maddamsetti, R., Subramanian, S., Weiss, R. & Benenson, Y:
A universal RNAi-based logic evaluator that operates in mammalian cells.
Nature Biotechnology 25, 795-801 (2007).