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Abstract Protein therapeutics are powerful tools in the fight against diabetes, cancers, growth disorders, and many other debilitating diseases. However, availability is limited due to cost and complications of production from living organisms. To make life‐saving protein therapeutics more available to the world, the possibility of magistral or point‐of‐care protein therapeutic production has gained focus. The recent invention and optimization of lyophilized “cell‐free” protein synthesis reagents and its demonstrated ability to produce highly active versions of FDA‐approved cancer therapeutics have increased its potential for low‐cost, single‐batch, magistral medicine. Here we present for the first time the concept of increased oxygen mass transfer in small‐batch, cell‐free protein synthesis (CFPS) reactions through air‐water foams. These “hydrofoam” reactions increased CFPS yields by up to 100%. Contrary to traditional protein synthesis using living organisms, where foam bubbles cause cell‐lysis and production losses, hydrofoam CFPS reactions are “cell‐free” and better tolerate foaming. Simulation and experimental results suggest that oxygen transfer is limiting in even small volume batch CFPS reactors and that the hydrofoam format improved oxygen transfer. This is further supported by CFPS reactions achieving higher yields when oxygen gas replaces air in the headspace of batch reactions. Improving CFPS yields with hydrofoam reduces the overall cost of biotherapeutic production, increasing availability to the developing world. Beyond protein therapeutic production, hydrofoam CFPS could also be used to enhance other CFPS applications including biosensing, biomanufacturing, and biocatalysis.
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Controlled Release of a Dual Zinc‐Sensing and Gene Regulating Small Molecule from DNA Micelles
Abstract Intracellular zinc ions are essential for various biological cell processes and are often dysregulated in many diseases de‐pending on their location, protein binding affinity, and concentration in the cell. Due to their prevalence in diseases, it is important to not only effectively sense but chelate the often excess amount of zinc in a cell to alleviate further disease progression. N, N, N′, N′‐tetrakis (2‐pyridinylmethyl)‐1,2‐ethanediamine (TPEN) is a selective zinc chelator but its water‐insoluble nature and general cytotoxicity limit its therapeutic potential. To address these challenges, TPEN loaded nucleic acid nanocapsules (TL‐NANs) were synthesized, and its dual ability to sense and suppress zinc levels intracellularly were evaluated. Additionally, TL‐NANs were incubated in lung cells and shown to down regulate Eotaxin, a protein up‐regulated during asthma, at significantly reduced concentrations of TPEN showcasing the therapeutic potential of this drug for asthma.
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- Award ID(s):
- 1847869
- PAR ID:
- 10418044
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- ChemBioChem
- Volume:
- 24
- Issue:
- 11
- ISSN:
- 1439-4227
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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