Giovanini, G.; Barros, L.R.C.; Gama, L.R.; Tortelli, T.C., Jr.; Ramos, A.F. A Stochastic Binary Model for the Regulation of Gene Expression to Investigate Responses to Gene Therapy. Cancers2022, 14, 633.
Giovanini, G.; Barros, L.R.C.; Gama, L.R.; Tortelli, T.C., Jr.; Ramos, A.F. A Stochastic Binary Model for the Regulation of Gene Expression to Investigate Responses to Gene Therapy. Cancers 2022, 14, 633.
Giovanini, G.; Barros, L.R.C.; Gama, L.R.; Tortelli, T.C., Jr.; Ramos, A.F. A Stochastic Binary Model for the Regulation of Gene Expression to Investigate Responses to Gene Therapy. Cancers2022, 14, 633.
Giovanini, G.; Barros, L.R.C.; Gama, L.R.; Tortelli, T.C., Jr.; Ramos, A.F. A Stochastic Binary Model for the Regulation of Gene Expression to Investigate Responses to Gene Therapy. Cancers 2022, 14, 633.
Abstract
In this manuscript we use an exactly solvable stochastic binary model for regulation of gene expression to analyse the dynamics of response to a treatment aiming to modulate the number of transcripts of RKIP gene. We demonstrate the usefulness of our method simulating three treatment scenarios aiming to reestablish RKIP gene expression dynamics towards pre-cancerous state: i. to increase the promoter’s ON state duration; ii. to increase the mRNAs’ synthesis rate; iii. to increase both rates. We show that the pre-treatment kinetic rates of ON and OFF promoter switching speeds and mRNA synthesis and degradation will affect the heterogeneity and time for treatment response. Hence, we present a strategy for reducing drug dosage by simultaneously targeting multiple kinetic rates. That enables a reduction of treatment response time and heterogeneity which in principle diminishes the chances of emergence of resistance to treatment. This approach may be useful for inferring kinetic constants related to expression of antimetastatic genes or oncogenes and on the design of multi-drug therapeutic strategies targeting master regulatory genes.
Keywords
RKIP expression regulation; Stochastic binary regulation of gene expression; Treatment targeting RKIP levels increase; Reduction of heterogeneity of treatment response
Subject
Biology and Life Sciences, Biophysics
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.