Methods and products for reawakening retrocyclins

Abstract

Products and methods are provided for the restoring the endogenous expression of theta-defensins, such as retrocyclin-1, in mamallian cells. The present invention also includes products and methods for inhibiting sexually transmitted virus entry, e.g., HIV-1 virus entry, into a mammalian cell via, for example, administering to a subject an amount of a read-through mediating agent sufficient to induce exogenous expression of an amount of retrocyclin nonapeptides in the mammalian cell.

The invention claimed is: 
     
         1 . A pharmaceutical composition for inhibiting HIV-1 cell entry comprising an amount of a read-through mediating agent effective to induce expression of a retrocyclin polypeptide in a mammalian cell. 
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the read-through mediating agent is an aminoglycoside effective to induce expression of a retrocyclin polypeptide in a mammalian cell. 
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein the read-through agent comprises gentamicin or tobramycin, or a combination of both. 
     
     
         4 . The pharmaceutical composition of  claim 1 , wherein the composition is a topical formulation comprised of a cream or ointment for application to mucosa. 
     
     
         5 . The pharmaceutical composition of  claim 4 , wherein the composition comprises 0.01% to 5.0% aminoglycoside. 
     
     
         6 . The pharmaceutical composition of  claim 4 , further comprising at least one of antifungal, vitamin, anti-inflammatory agent, antimicrobial, analgesic, surfactant, moisturizer, stabilizer, preservative, antiseptic, thickener, lubricant, or skin penetration enhancer. 
     
     
         7 . The pharmaceutical composition of  claim 4 , wherein the composition comprises a skin penetration enhancer. 
     
     
         8 . A delivery and expression vector for transfecting a cell with an expression construct encoding a retrocyclin polypeptide, wherein the expression construct comprises a polynucleotide sequence encoding SEQ. ID. NO: 8 or SEQ. ID. NO: 9, or variants thereof. 
     
     
         9 . The delivery and expression vector of  claim 8 , wherein the expression construct comprises SEQ. ID. NO: 1, SEQ. ID NO: 2, SEQ. ID. NO: 3, or SEQ. ID NO: 4, or variants thereof. 
     
     
         10 . A method for reducing virus entry into a host cell of a mammalian subject comprising administering to the mammalian subject an amount of an expression construct encoding a retrocyclin polypeptide, wherein the expression construct comprises a polynucleotide sequence encoding SEQ. ID. NO: 8 or SEQ. ID. NO: 9, or variants thereof.