title: Engineering Synthetically Modified Insulin for Glucose-Responsive Diabetes Therapy.
abstract: Though a suite of different insulin variants have been used clinically to provide greater control over pharmacokinetics, no clinically used insulin can tune its potency and/or bioavailability in a glucose-dependent manner. In order to improve therapy for diabetic patients, a vision has been the development of autonomous closed-loop approaches. Toward this goal, insulin has been synthetically modified with glucose-sensing groups or groups that can compete with free glucose for binding to glucose-binding proteins and evaluated in pre-clinical models. Specifically, it was demonstrated that site-specific modification of insulin with phenylboronic acid can result in glucose-responsive activity, leading to faster recovery in diabetic mice following a glucose challenge but with less observed hypoglycemia in healthy mice. This strategy, along with several others being pursued, holds promise to improve the fidelity in glycemic control with routine insulin therapy.
authors: David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge MA 02139, USA; Department of Anesthesiology, Boston Children's Hospital, Boston, MA 02115, USA.
authors: Matthew J
authors: MJ
authors: Webber
authors: David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge MA 02139, USA; Department of Anesthesiology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge MA 02139, USA; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge MA 02139, USA; Harvard-MIT Division of Health Science and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors: Daniel G
authors: DG
authors: Anderson
authors: David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge MA 02139, USA; Department of Anesthesiology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge MA 02139, USA; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge MA 02139, USA; Harvard-MIT Division of Health Science and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors: Robert
authors: R
authors: Langer
keywords: Concanavalin A; bioartificial pancreas; bionic pancreas; diabetes; drug delivery; fully synthetic pancreas; lectin; phenylboronic acid