Cell-Free DNA Circuits — Design Blueprint: Marker-Activated Molecular System Without Living Cells
Year: 2026
Type: article
Abstract: DESIGN BLUEPRINT — SIMULATED, NOT MEASURED — NOT BUILT. Design blueprint derived from 'Cell-Free DNA Circuits as the Safer Injectable: A Design Study of a Marker-Activated Molecular System Without Living Cells' (DOI: 10.5281/zenodo.24109036). Specifies an injectable DNA-only circuit that circulates inert and activates only inside cells presenting two marker sequences, by sequential toehold exchange. Architecture and design parameters (10 mg dose of a 90 kDa, 12 nm assembly; 6.69 x 10^16 copies; 37.0 nM initial plasma concentration), functional production outline with quality-control checkpoints, and operating budgets: 3,346 cytosolic copies per target cell, AND discrimination 61.7 versus 7.86 single-marker, total healthy-cell false activation 3.66%, effective half-life 4.36 hours with a 14.5-hour working window, 97.8% cleared in 24 hours, payload margin 3.51, and a hard payload ceiling of 2.22 x 10^-6 mol per dose. Give-ups printed at full size: no expansion, no migration (228 micrometre diffusion reach), no memory, and therapeutic failure if under 0.143% of the dose reaches the target. Safety case prints immune-recognition risk as NOT BUDGETED, stopping conditions in the source's figures, acceptance criteria on measured values, and explicit non-claims: nothing built, synthesised, or tested.
Author: Aldred, William Alexander
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7225739597