In vivo Endocrine Secretion of Prostacyclin Following Expression of a Cyclooxygenase-1/Prostacyclin Fusion Protein in the Salivary Glands of Rats Via Nonviral Gene Therapy

Human Gene Therapy
Zhimin WangMichael J Passineau

Abstract

Pulmonary arterial hypertension (PAH) is a progressive disease that culminates in right heart failure and death. Prostacyclin (PGI2) and its derivatives are effective treatments for PAH when administered as continuous parenteral infusions. This treatment paradigm requires medical sophistication, and patients are at risk for complications from an indewelling catheter; drug interruptions may result in rebound pulmonary hypertension and death. We hypothesized that the salivary gland can be repurposed into an endogenous production site for circulating PGI2 through the expression of a fusion protein embodying cyclooxygenase-1 (Cox1) and prostacyclin synthase (PGIS) domains. We utilized ultrasound-assisted gene transfer, a nonviral gene transfer strategy that achieves robust gene transfer to the salivary gland. We initially found that Cox1-PGIS expression in livers of mice using an adenoviral vector dramatically increased circulating PGI2 relative to untreated rats or rats treated with PGIS alone. We then utilized ultrasound-assisted gene transfer to express Cox1-PGIS in the submandibular glands of rats and showed a significant elevation of circulating PGI2 that corresponded to approximately 30% of that seen in humans undergoing intr...Continue Reading

References

Jul 9, 1992·The New England Journal of Medicine·B W ChristmanJ E Loyd
Jan 1, 1994·European Journal of Clinical Pharmacology·W CawelloH W Seyberth
Dec 10, 1999·Human Gene Therapy·B J BaumJ Chao
Nov 1, 1962·Journal of Atherosclerosis Research·J J LALICH, L A EHRHART
Apr 2, 2008·The European Respiratory Journal·M Gomberg-Maitland, H Olschewski
Jun 12, 2008·Biochemical and Biophysical Research Communications·Yuval SamuniBruce J Baum
May 29, 2010·Gene Therapy·M J PassineauR L Benza
Jul 19, 2011·Biochimica Et Biophysica Acta·Yuval Samuni, Bruce J Baum
Nov 22, 2014·Molecular Therapy. Methods & Clinical Development·Ramaz GeguchadzeMichael J Passineau
Jul 8, 2015·Expert Opinion on Biological Therapy·Bruce J BaumChangyu Zheng
Jan 11, 2016·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Caroline O'ConnellOlivier Sitbon

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection
ELISA
reverse transcription PCR
PCR

Software Mentioned

Stata

Related Concepts

Related Feeds

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.