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Updated: Jul 1, 2026

Analysis of Protein-protein Interactions and Co-localization Between Components of Gap, Tight, and Adherens Junctions in Murine Mammary Glands
Published on: May 30, 2017
Regulation of protein secretion through controlled aggregation in the endoplasmic reticulum
V M Rivera1, X Wang, S Wardwell
1ARIAD Gene Therapeutics, 26 Landsdowne Street, Cambridge, MA 02139, USA. vrivera@ariad.com
Abstract:
A system for direct pharmacologic control of protein secretion was developed to allow rapid and pulsatile delivery of therapeutic proteins. A protein was engineered so that it accumulated as aggregates in the endoplasmic reticulum. Secretion was then stimulated by a synthetic small-molecule drug that induces protein disaggregation. Rapid and transient secretion of growth hormone and insulin was achieved in vitro and in vivo. A regulated pulse of insulin secretion resulted in a transient correction of serum glucose concentrations in a mouse model of hyperglycemia. This approach may make gene therapy a viable method for delivery of polypeptides that require rapid and regulated delivery.
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