Computational gene

The structural part is a naturally occurring gene, which is used as a skeleton to encode the input and the transitions of the automaton (Fig.

The constants and the design parameters are linked by several logical and biochemical constraints (e.g., encoded automata theoretic variables must not be recognized as splicing junctions).

If the input is accepted, the output encodes a double stranded DNA (dsDNA) molecule, a functional gene which should be successfully integrated into the cellular transcription and translation machinery producing a wild type protein or an anti-drug (Fig.

A single disease-related mutation can be then diagnosed and treated by the following diagnostic rule: if protein X_mutated_at_codon_Y then produce_drug fi (1)Such a rule might be implemented by a molecular automaton consisting of two partially dsDNA molecules and one ssDNA molecule, which corresponds to the disease-related mutation and provides a molecular switch for the linear self-assembly of the functional gene (Fig.

In this way, computational genes might allow implementation in situ of a therapy as soon as the cell starts developing defective material.

Although mechanistically simple and quite robust on molecular level, several issues need to be addressed before an in vivo implementation of computational genes can be considered.

[8] Some results show that nuclear localisation signals can be irreversibly linked to one end of the oligonucleotides, forming an oligonucleotide-peptide conjugate that allows effective internalisation of DNA into the nucleus.

Figure 1: Design of a computational gene
Figure 2: Diagnostics of pathogenic mutations
Figure 3: Therapy of pathogenic mutations