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

Bowyer, Jack; Chakravarti, Deboki; Wong, Wilson; Bates, Declan G.

doi:10.1049/enb.2019.0020

Cited by 2 publications

(2 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our 2-input BLADE model is based on the structure of an existing model of a tyrosine recombinasebased flip-excision (FLEx) switch [46]. The model is comprised of one excision reaction per state transition, with the exception of the transition from Z 00 to Z 10 , which involves two pairs of Crespecific loxP attachment sites and hence two excision reactions.…”

Section: A Mechanistic Model Of the Blade Platformmentioning

confidence: 99%

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

Bowyer

Ding

Weinberg³

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

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. After calibrating the model on experimental data from two circuits, we demonstrate close agreement between model outputs and data on the other 111 circuits that have so far been experimentally constructed using the 2-input BLADE platform. Model simulations of the remaining 143 circuits that have yet to be tested experimentally predict excellent performance of the 2-input BLADE platform across the range of possible circuits.Circuits from both the tested and untested subsets that perform less well consist of a disproportionally high number of STOP sequences. Model predictions suggested that circuit performance declines with a decrease in recombinase expression and new experimental data was generated that confirms this relationship.

show abstract

Section: A Mechanistic Model Of the Blade Platformmentioning

confidence: 99%

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

Bowyer

Ding

Weinberg³

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Our 2-input BLADE model is based on the structure of an existing model of a tyrosine recombinase-based flip-excision (FLEx) switch [45]. The model is comprised of one excision reaction per state transition, with the exception of the transition from Z 00 to Z 10 , which involves two pairs of Cre-specific loxP attachment sites and hence two excision reactions.…”

Section: A Mechanistic Model Of the Blade Platformmentioning

confidence: 99%

Untitled

View full text Add to dashboard Cite

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

Cited by 2 publications

References 54 publications

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

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

Untitled

Contact Info

Product

Resources

About