LOCAL-DELIVERY OF C-MYB ANTISENSE OLIGONUCLEOTIDES DURING BALLOON ANGIOPLASTY

Intraluminal delivery of antisense oligonucleotides to c-myb was asses sed following balloon angioplasty in swine peripheral arteries, Succes sful delivery and intramural persistence of oligonucleotide for over 2 4 h were demonstrated following angioplasty with hydrogel balloons coa ted with P-32-labeled antisense. Delivery of fluorescein-labeled antis ense demonstrated further localization within the arteria( media and i ntracellularly, Preliminary in vitro studies demonstrated the feasibil ity of inhibition of porcine lymphocyte proliferation using the murine antisense to c-myb, Twelve iliac or carotid arteries underwent angiop lasty with antisense-coated balloons, while the contralateral vessels underwent angioplasty with the same-sized balloons coated with the com plementary sense strand. Six to seven days later, dilated arterial seg ments were surgically isolated, In 10 of 12 vessel pairs, antisense-tr eated vessels demonstrated less cellular proliferation than did contra lateral sense-treated vessels, as assessed by quantitative immunohisto chemical staining of proliferating cell nuclear antigen, and smooth mu scle cell proliferation was reduced 18% in antisense-treated vessels c ompared to the contralateral sense-treated vessels (PCNA-positive nucl ear area: 7.7 +/- 4.9% vs, 9.3 +/- 5.2%, P < 0.04). Intraluminal deliv ery of antisense oligonucleotides to c-myb is feasible with a catheter -based system and may reduce smooth muscle cell proliferation followin g arterial injury. (C) 1997 Wiley-Liss, Inc.