Glucagon-like peptide-2 (GLP-2) is a naturally occurring 33 amino acid peptide, with t1/2 of 6-7 min. This peptide is produced by L cells of small intestine and has several important functions, such as increasing intestinal absorption, stimulating intestinal growth, reducing bone breakdown and impacting gastric and intestinal motility. It is well known that individuals with short bowel syndrome benefit from exogenous GLP-2 to improve intestinal absorption.Native peptides have been difficult to develop into drugs because of their short half-life, poor metabolic stability and rapid clearance. Manufactured peptides frequently require structural modification and, long-acting formulations. Moreover, the treatment with such peptides frequently uses high doses, which can lead to off-target effects such as nausea and vomiting in some patients. As an alternative, we developed a novel approach that allows our TARGT™ (Transduced Autologous Restorative Gene Therapy) technology to produce and secrete peptides such as GLP-2.The TARGT™ system is an ex-vivo gene therapy, which we have now demonstrated is capable of providing autologous, continuous peptide therapies, at physiological ranges. Our group previously demonstrated such findings for certain proteins. In one set of experiments described herein, the TARGT™ system consists of several 2 × 30 mm biopsies of dermal tissue (Micro-Organ, MO), extracted under local anesthetic followed by fibroblast transduction with a Helper-Dependent Adenoviral Vector (HDAd) containing a novel GLP-2 gene expression cassette. After culture, and measurement of peptide production, one or more transduced MOs (TARGTs™) are re-implanted into the patient as required to achieve the desired dose. The system allows dose flexibility and the TARGTs™ may be added or removed according to in-vivo secretion levels.Pre-clinical studies, using this novel technology, showed GLP-2 TARGT (TARGTGLP-2) in-vitro secretion levels of tens of micrograms per day. Preliminary data from in-vivo SCID mice experiments confirms that TARGT-secreted human GLP-2 analog reaches the mouse blood stream and exhibits a sustained secretion profile similar to tho se observed and reported with other proteins using the TARGT™ technology (e.g. EPO, IFNα). In addition, in-vivo SCID mice and rat experiments suggest that TARGT™ secreted GLP-2 analog is active, and increases intestinal villous height and intestinal crypt cell proliferation rate.Data obtained so far suggests that TARGTGLP-2 may provide a favorable PK profile and physiologic levels of continuous GLP-2 for extended periods of time, avoiding supra-physiological peak serum concentration and achieving continuous coverage with less exposure compared to exogenous GLP-2 injections. The current results suggest that the TARGT™ platform is a promising novel therapy for short bowel syndrome and potentially other diseases of endogenous protein/peptide deficiency.