A mechanistic model of the BLADE platform predicts performance characteristics of 256 different synthetic DNA recombination circuits.

Boolean logic and arithmetic through DNA excision (BLADE) is a recently developed platform for implementing inducible and logical control over gene expression in mammalian cells, which has the potential to revolutionise cell engineering for therapeutic applications. This 2-input 2-output platform can implement 256 different logical circuits that exploit the specificity and stability of DNA recombination. Here, we develop the first mechanistic mathematical model of the 2-input BLADE platform based on Cre- and Flp-mediated DNA excision.

Mechanistic modelling of tyrosine recombination reveals key parameters determining the performance of a CAR T cell switching circuit.

Inducible genetic switches based on tyrosine recombinase-based DNA excision are a promising platform for the regulation and control of chimeric antigen receptor (CAR) T cell activity in cancer immunotherapy. These switches exploit the increased stability of DNA excision in tyrosine recombinases through an inversion-excision circuit design. Here, the authors develop the first mechanistic mathematical model of switching dynamics in tyrosine recombinases and validate it against experimental data through both global optimisation and statistical approximation approaches.

Modeling the architecture of the regulatory system controlling methylenomycin production in .

Background: The antibiotic methylenomycin A is produced naturally by Streptomyces coelicolor A3(2), a model organism for streptomycetes. This compound is of particular interest to synthetic biologists because all of the associated biosynthetic, regulatory and resistance genes are located on a single cluster on the SCP1 plasmid, making the entire module easily transferable between different bacterial strains. Understanding further the regulation and biosynthesis of the methylenomycin producing gene cluster could assist in the identification of motifs that can be exploited in synthetic regulatory systems for the rational engineering of novel natural products and antibiotics.