Abstract
Wearable smart electronic devices, such as smart watches, are generally equipped with green-light-emitting diodes, which are used for photoplethysmography to monitor a panoply of physical health parameters. Here, we present a traceless, green-light-operated, smart-watch-controlled mammalian gene switch (Glow Control), composed of an engineered membrane-tethered green-light-sensitive cobalamin-binding domain of Thermus thermophilus (TtCBD) CarH protein in combination with a synthetic cytosolic TtCBD-transactivator fusion protein, which manage translocation of TtCBD-transactivator into the nucleus to trigger expression of transgenes upon illumination. We show that Apple-Watch-programmed percutaneous remote control of implanted Glow-controlled engineered human cells can effectively treat experimental type-2 diabetes by producing and releasing human glucagon-like peptide-1 on demand. Directly interfacing wearable smart electronic devices with therapeutic gene expression will advance next-generation personalized therapies by linking biopharmaceutical interventions to the internet of things.
Highlights
Wearable smart electronic devices, such as smart watches, are generally equipped with green-light-emitting diodes, which are used for photoplethysmography to monitor a panoply of physical health parameters
To take this idea forward, we focus on the cobalamin-binding domain (CBD) of the CarH protein of T. thermophilus (TtCBD)[27], which assembles as a dimer of dimers in the dark when bound to the 5’-deoxyadenosylcobalamin chromophore, an active coenzyme form of vitamin B1228
As a proof-of-concept, we show that subcutaneously implanted microencapsulated Glowcontrolled engineered human cells can effectively treat diabetes and associated symptoms, including postprandial hyperglycemia, insulin resistance, fasting blood glucose levels, and obesity, in a mouse model of type-2 diabetes by means of percutaneously remote-controlled release of human glucagon-like peptide-1 using programmed green-light illumination
Summary
Wearable smart electronic devices, such as smart watches, are generally equipped with green-light-emitting diodes, which are used for photoplethysmography to monitor a panoply of physical health parameters. The green-light-emitting functionality of smart wearable electronic devices has been used exclusively to record health parameters, but we considered that it might be feasible to use this functionality to achieve light-inducible percutaneous remote control of therapeutic protein production in subcutaneously implanted cells in a user-defined or automatic manner. To take this idea forward, we focus on the cobalamin-binding domain (CBD) of the CarH protein of T. thermophilus (TtCBD)[27], which assembles as a dimer of dimers in the dark when bound to the 5’-deoxyadenosylcobalamin chromophore, an active coenzyme form of vitamin B1228. As a proof-of-concept, we show that subcutaneously implanted microencapsulated Glowcontrolled engineered human cells can effectively treat diabetes and associated symptoms, including postprandial hyperglycemia, insulin resistance, fasting blood glucose levels, and obesity, in a mouse model of type-2 diabetes by means of percutaneously remote-controlled release of human glucagon-like peptide-1 (hGLP1) using programmed green-light illumination
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