Jamili, E;
Dua, V;
(2018)
Optimal Model-Based Control of Non-Viral siRNA Delivery.
Biotechnology & Bioengineering
10.1002/bit.26596.
(In press).
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Abstract
Further quantitative understanding of the biological effects and mechanisms involved in cellular and intracellular delivery of nucleic acid materials is critical to produce clinical applications in the area of gene therapy. Several modeling approaches have been used in this field; however, a comprehensive approach that integrates all the key pharmacological issues into a holistic framework that is applicable for in vivo conditions is still lacking. This contribution presents a pharmacokinetic/pharmacodynamic model-based control study of non-viral siRNA delivery describing the dynamics of the delivery process and takes into account the main multi-objective optimization issues such as efficacy and toxicity, as well as the effect of uncertainty in cell doubling time. The methodology developed in this work is used to predict the optimal dosage injection rate and optimal intracellular exposure of siRNAs in order to improve pharmacological effects before cell division occurs. The present analysis successfully provides quantitative predictions of non-viral siRNA activity paving the path for further experimental work to probe more efficient delivery systems. This article is protected by copyright. All rights reserved.
| Type: | Article |
|---|---|
| Title: | Optimal Model-Based Control of Non-Viral siRNA Delivery |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/bit.26596 |
| Publisher version: | http://dx.doi.org/10.1002/bit.26596 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Cell division, Efficacy, Optimal control, Pharmacokinetic/pharmacodynamic modeling, Toxicity, siRNA delivery |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Chemical Engineering |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10046621 |
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