摘要 |
<p>The present invention concerns the introduction of specific alterations in the genes that encode three apolipoproteins, Apo A1, Apo B and Apo E. The alternations in Apo A1 introduce a cysteine residue so the disulfide cross-linked Apo A1 homodimers and Apo A1/A2 heterodimers can be formed. The alterations in Apo B introduce stop codons or frame shift mutations that cause the production of a truncated Apo B protein. The alterations in Apo E introduce specific point mutations that have been identified as protective. The production in the liver of a subject of these altered proteins reduces the risk of the subjects developing atherosclerosis. In one embodiment the genetic alterations are introduced by use of chimeric, mixed RNA/DNA, duplex oligonucleotides.</p> |