Zamecnik P C, Goodchild J, Taguchi Y, Sarin P S
Proc Natl Acad Sci U S A. 1986 Jun;83(12):4143-6. doi: 10.1073/pnas.83.12.4143.
The possibility of using oligodeoxynucleotides complementary to viral RNA or proviral DNA to inhibit the replication of human T-cell lymphotropic virus type III (HTLV-III) [the etiological agent of acquired immunodeficiency syndrome (AIDS)] in cultured human cells was addressed by studying the association of 32P-labeled oligodeoxynucleotides with mammalian cellular components. The results indicated that exogenous oligodeoxynucleotides at 20 microM became associated with the membrane/cytosol fractions of the cell in amounts approximating 1.5 microM. Oligodeoxynucleotides complementary to a region close to the tRNALys primer binding site on HTLV-III RNA and others complementary to HTLV-III mRNA donor or acceptor splice sites inhibited viral replication (assayed as reverse transcriptase) and gene expression (assayed as virus-encoded proteins p15 and p24) by as much as 95%. Use of control (random) oligodeoxynucleotides suggests that the antiviral effects were specific. Although these results pertain to HTLV-III-infected cells in tissue culture, rather than to AIDS patients, they nevertheless point to a therapeutic potential of the complementary oligodeoxynucleotide ("hybridization competition" or "hybridon") approach in the treatment of patients with AIDS and AIDS-related complex.
通过研究32P标记的寡脱氧核苷酸与哺乳动物细胞成分的结合情况，探讨了使用与病毒RNA或前病毒DNA互补的寡脱氧核苷酸来抑制人类III型嗜T细胞病毒（HTLV-III）[获得性免疫缺陷综合征（AIDS）的病原体]在培养的人类细胞中复制的可能性。结果表明，20微摩尔的外源寡脱氧核苷酸与细胞的膜/胞质溶胶部分结合，结合量约为1.5微摩尔。与HTLV-III RNA上靠近tRNALys引物结合位点的区域互补的寡脱氧核苷酸以及与HTLV-III mRNA供体或受体剪接位点互补的其他寡脱氧核苷酸，可将病毒复制（以逆转录酶测定）和基因表达（以病毒编码蛋白p15和p24测定）抑制多达95%。使用对照（随机）寡脱氧核苷酸表明抗病毒作用具有特异性。尽管这些结果适用于组织培养中的HTLV-III感染细胞，而非艾滋病患者，但它们仍然指出了互补寡脱氧核苷酸（“杂交竞争”或“杂交体”）方法在治疗艾滋病和艾滋病相关综合征患者方面的治疗潜力。
