Effect of adeno-associated virus-mediated transfer of low density lipoprotein receptor gene on treatment of hypercholesterolemia

Low density lipoprotein receptor (LDL\|R) plays an important role in removing LDL from plasma and preventing producing atherosclerosis. To test hepatic reconstitution of LDL\|R expression is sufficient for metabolic correction of subjects with hypercholesterolemia; a recombinant adeno\|associated virus (rAAV) carrying the human LDL receptor cDNA (AAV/LDL\|R) was constructed. Using adenosome, a complex of adenoviral capsid protein and liposome, to transfer the rAAV into livers of rabbits with experimental hypercholesterolemia could elicit the production of LDL\|R and lower plasma cholesterol level. These results demonstrate that AAV\|mediated transfer of LDL\|R gene may provide an alternative means to gene therapy of hypercholesterolemia.