| 摘要 |
<p>Human papillomaviruses (HPV) have been strongly implicated as important cofactors in the development of several human malignancies, particularly anogenital carcinomas. Products arising from the E6 and E7 open reading frames (ORFs) from PHV-16, a serotype commonly associated with human cervical carcinoma, are essential for viral transformation. To develop a novel treatment for this disease, ribozymes were designed to cleave HPV-16 E6 and E7 ORF transcripts in proximity to their translational start sites ('AUG'). Cleavage sites occur immediately 3' to nucleotides 110 and 558 of the viral genomic DNA, respectively. Oligonucleotides corresponding to these ribozymes were synthesized and inserted into a eucaryotic viral vector derived from the nonpathogenic parvovirus, adeno-associated virus (AAV). Ribozyme transcription from this vector, termed CWRT7:SVN, is under control of both the highly active Rous sarcoma virus LTR and bacteriophage T7 promoters. T7 transcripts of the E6 and E7 ribozymes efficiently cleaved their cognate targets in vitro under a variety of conditions, including physiological temperature.</p> |
