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A simple model for gene targeting

Tommi Ratilainen (Institutionen för fysikalisk kemi) ; Per Lincoln (Institutionen för fysikalisk kemi) ; Bengt Nordén (Institutionen för fysikalisk kemi)
Biophysical Journal (0006-3495 ). Vol. 81 (2001), 5, p. 2876-2885.
[Artikel, refereegranskad vetenskaplig]

Sequence-specific binding to genomic-size DNA sequences by artificial agents is of major interest for the development of gene-targeting strategies, gene-diagnostic applications, and biotechnical tools. The binding of one such agent, peptide nucleic acid (PNA), to a randomized human genome has been modeled with statistical mass action calculations. With the length of the PNA probe, the average per-base binding constant k(0), and the binding affinity loss of a mismatched base pair as main parameters, the specificity was gauged as a "therapeutic ratio" G = maximum safe [PNA](tot)/minimal efficient [PNA](tot). This general, though simple, model suggests that, above a certain threshold length of the PNA, the microscopic binding constant k(0) is the primary determinant for optimal discrimination, and that only a narrow range of rather low k(0) values gives a high therapeutic ratio G. For diagnostic purposes, the value of k(0) could readily be modulated by changing the temperature, due to the substantial DeltaH(o) associated with the binding equilibrium. Applied to gene therapy, our results stress the need for appropriate control of the binding constant and added amount of the gene-targeting agent, to meet the varying conditions (ionic strength, presence of competing DNA-binding molecules) found in the cell.

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Denna post skapades 2011-01-05. Senast ändrad 2011-07-01.
CPL Pubid: 132482


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Institutionen för fysikalisk kemi (1900-2003)


Nanovetenskap och nanoteknik
Fysikalisk kemi

Chalmers infrastruktur