Transfer of a gene encoding the anticandidal protein histatin 3 to salivary glands

Human Gene Therapy
B C O'ConnellB J Baum

Abstract

Mucosal candidiasis, the most common opportunistic fungal infection in human immunodeficiency virus (HIV)-infected patients, is an early sign of clinically overt acquired immunodeficiency syndrome (AIDS) and an important cause of morbidity, particularly in HIV-infected children. The appearance of azole-resistant strains of Candida albicans had made clinical management of candidiasis increasingly difficult. We propose a novel approach to the management of candidal infections that involves the use of naturally occurring antifungal proteins, such as the histatins. Histatins are a family of small proteins that are secreted in human saliva. We have constructed recombinant adenovirus vectors that contain the histatin 3 cDNA. These vectors are capable of directing the expression of histatin 3 in the saliva of rats at up to 1,045 micrograms/ml, well above the levels found in normal human saliva. The adenovirus-directed histatin demonstrated a 90% candidacidal effect in the timed-kill assay against both fluconazole-susceptible and fluconazole-resistant strains of C. albicans and inhibited germination by 45% in the same strains. These studies suggest that a gene transfer approach to overexpress naturally occurring antifungal proteins may...Continue Reading

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Citations

Mar 28, 2001·The Journal of Gene Medicine·L BaccagliniB J Baum
Dec 10, 1999·Human Gene Therapy·B J BaumJ Chao
May 13, 2003·Tissue Engineering·Stephen M WarrenMichael T Longaker
Oct 26, 1999·European Journal of Dental Education : Official Journal of the Association for Dental Education in Europe·B J Baum, B C O'Connell
Nov 18, 2000·Antimicrobial Agents and Chemotherapy·M EdgertonJ A Bruenn
Oct 19, 2004·Clinical Microbiology Reviews·Louis de RepentignyPaul Jolicoeur
Jun 19, 2001·Biological Chemistry·W van 't HofA V Amerongen
Feb 2, 2002·Journal of Drug Targeting·A T HoqueB J Baum
Jul 8, 2015·Expert Opinion on Biological Therapy·Bruce J BaumChangyu Zheng
Mar 15, 2006·Dental Clinics of North America·Ana P CotrimBruce J Baum
May 9, 2009·The Journal of Gene Medicine·Gabor Z RaczBruce J Baum
Jan 1, 2014·Oral Diseases·B J Baum
Feb 24, 2005·Journal of Dentistry·Michael W J DoddsChih-Ko Yeh
Nov 30, 2004·Trends in Molecular Medicine·Bruce J BaumJianghua Wang
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Jul 9, 2003·Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology·Brian C O'ConnellBruce J Baum

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