Hyaluronic acid mediated adenoviral transduction

Abstract

The present invention provides methods of treatment of adenoviral mediated disease, improved methods for transducing cells with adenoviral and related vectors, and improved methods of gene therapy utilizing such methods.

1 . A method of treating adenoviral disease comprising: 
 (a) identifying a subject in need of such treatment;    (b) administering to the subject a composition comprising low molecular weight hyaluron in an amount sufficient to inhibit or prevent adenoviral disease.    
   
   
       2 . (canceled)  
   
   
       3 . The method of  claim 2 , wherein the hyaluron has an average molecular weight of less than 750,000 Da.  
   
   
       4 . The method of  claim 2 , wherein the hyaluron has an average molecular weight within the range of 50,000 Da to 750,000 Da.  
   
   
       5 . The method of  claim 4 , wherein the hyaluron has an average molecular weight of from 50,000 Da to 300,000 Da.  
   
   
       6 . The method of  claim 1 , wherein the composition comprises degradation products of high molecular weight hyaluron.  
   
   
       7 . (canceled)  
   
   
       8 . The method of  claim 1 , wherein the subject is a human.  
   
   
       9 . A method for inhibiting adenovirus infection comprising administering to a cell a composition comprising an adenovirus inhibitor comprising low molecular weight hyaluron in an amount sufficient to inhibit the progress of adenovirus infection.  
   
   
       10 - 41 . (canceled)  
   
   
       42 . The method of  claim 1 , wherein the composition comprises degradation products of hyaluron and degradation products of vitreous.  
   
   
       43 . The method of  claim 42 , wherein the degradation products of vitreous comprise out of date vitreous.  
   
   
       44 . The method of  claim 1 , wherein the concentration of hyaluron in the composition is 10 micrograms/100μ to 240 micrograms/100 μl.  
   
   
       45 . The method of  claim 1 , further comprising administering one or more secondary therapeutic agents.  
   
   
       46 . The method of  claim 1 , wherein administering comprises intravenous, intradermal, intraarterial, intraperitoneal, intralesional, intracranial, intraarticular, intrapostatic, intrapleural, intratracheal, intranasal, intravitreal, intravaginal, intrarectal, topical, intratumoral, intramuscular, intraperiotoneal, subcutaneous, subconjunctival, intravesical, mucosal, intrapericardial, intraumbilical, intraocular, oral, local, or aerosol administration.  
   
   
       47 . The method of  claim 1 , wherein the concentration of degradation products in the composition is at least about 0.1% by weight.  
   
   
       48 . The method of  claim 47 , wherein the concentration of degradation products in the composition is between about 2% to about 75% by weight.  
   
   
       49 . The method of  claim 1 , further comprising administering to the subject a composition comprising an antibody specific to CD44.  
   
   
       50 . The method of  claim 49 , wherein the antibody is a monoclonal antibody.  
   
   
       51 . The method of  claim 49 , wherein the antibody is KM114.  
   
   
       52 . The method of  claim 6 , wherein the degradation products of high molecular weight hyaluron comprise out of date hyaluron.  
   
   
       53 . The method of  claim 9 , wherein the adenoviral inhibitor comprises degradation products of high molecular weight hyaluron.  
   
   
       54 . The method of  claim 9 , wherein the adenoviral inhibitor has an average molecular weight of less than 750,000 Da.  
   
   
       55 . The method of  claim 53 , wherein the degradation products of high molecular weight hyaluron comprise out of date hyaluron.