Table 2.
Model parameters
| Name | Description (units) | Determination | Value |
|---|---|---|---|
| max | Maximum number of cells (#) | Determined experimentally | Fit to each system |
| partition | Effective fraction of dose available to target cells | Estimated from experimental data | 1 × 10−3 |
| rtot | Total available amount of RISC protein complexes (# L−1) | Literature (42–44) | 1.9 × 1015 |
| Ve | Extracellular volume (L) | Specified experimentally in vitro, Estimated from experimental data and literature (45,46) | 2 × 10−41 × 10−5 |
| Vi | Intracellular volume (L) | Literature (47) | 4 × 10−12 |
| Vp | Plasma volume, mouse (L) | Literature (48) | 1.5 × 10−3 |
| kbloodbind | Complex binding to blood components (h−1) | Estimated from experimental data | 1 × 10−4 |
| kblooddis | Complex dissociation from blood components (h−1) | Estimated from experimental data | 1 × 10−2 |
| kcleavage | Cleavage of target mRNA by activated RISC complex (h−1) | Literature (44) | 7.2 |
| kdegendna | Endosomal siRNA degradation (h−1) | Literature (32–34,49) | 5 × 10−1 |
| kdeginna | Intracellular siRNA degradation (h−1) | Estimated from experimental data and literature (33) | 2.9 × 10−2 |
| kdegmRNA | Target mRNA degradation (h−1) | Literature (50–53) | 2 |
| kdegprot | Target protein degradation, Luciferase (h−1) | Literature (25) | 3.5 × 10−1 |
| kdegRISC | Activated RISC complex degradation (h−1) | Estimated from experimental data | 7.7 × 10−2 |
| kdisRISC | Dissociation of activated RISC complex (h−1) | Chosen to be negligible once activated RISC is formed | 1 × 10−9 |
| kdisRISCm | Dissociation of activated RISC complex and target mRNA (h−1) | Literature (42–44) | 1 |
| kelimec | Extracellular complex degradation (h−1) | Estimated from experimental data | 8.7 × 10−2 |
| 2.9 × 10−2 | |||
| kelimpl | Plasma complex degradation (h−1) | Estimated from experimental data | 5.8 × 10−2 |
| kescendna | Endosomal escape for siRNA (h−1) | Estimated from experimental data and literature (54) | 6 × 10−2 |
| kescendvec | Endosomal escape for complex (h−1) | Estimated from experimental data and literature (54) | 1 × 10−2 |
| kformmRNA | Formation of target mRNA (# L−1 h−1) | Literature (50,51) | 5.2 × 1013 |
| kformprot | Formation of target protein (h−1) | Literature (50,51) | 5.2 × 102 |
| kformRISC | Formation of activated RISC complex (L #−1 h−1) | Estimated from experimental data | 2 × 10−19 |
| kformRISCm | Formation of activated RISC/mRNA complex (L #−1 h−1) | Literature (42–44) | 1.1 × 1014 |
| kgrowth | Cell growth rate (h−1) | Determined experimentally | Fit to each system |
| kint | Internalization (h−1) | Literature (12,13,55) | 1 × 10−55 × 10−7 |
| ktransblood | Transport from plasma to extracellular fluid (h−1) | Estimated from experimental data | 1 × 10−2 |
| kunpackcyt | Cytosolic complex unpackaging (h−1) | Estimated from experimental data | 5 × 10−16 × 10−2 |
| kunpackend | Endosomal complex unpackaging (h−1) | Estimated from experimental data | 1 × 10−41 × 10−3 |
For parameters common to both in vitro and in vivo applications, the in vivo parameter values are shown in italics below the in vitro parameter values.