Antisense DNA and RNA: progress and prospects.

Walder, Joseph A.

doi:10.1101/gad.2.5.502

Cited by 64 publications

(18 citation statements)

References 10 publications

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“…It has been used experimentally to modulate gene activity in vivo in plants (Rodermel et al, 1988, Rogers, 1988Smith et al, 1988 ;Cuozzo et al, 1988 ;Hemenway et al, 1988) and animals (Giebelhaus et al, 1988). The mechanism of inhibition may include interference with RNA processing or inhibition of the initiation of translation (Munroe, 1988;Walder, 1988;Cotten et al, 1989). For this reason, there is a possibility that one could exploit antisense nucleic acid to inhibit the replication of viruses m vivo without affecting the expression of host genes.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of human immunodeficiency virus replication in cell culture by endogenously synthesized antisense RNA

Rhodes

James

1990

Journal of General Virology

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Antisense RNA, which has a sequence complementary to mRNA, may provide the basis for antiviral therapies of high selectivity. We have explored the inhibitory effect of six antisense RNAs upon the replication of human immunodeficiency virus (HIV) in cell culture. We chose regions of the HIV genome to test whether sequences required for splicing or for translation initiation were more susceptible to antisense RNA interference. Our results suggest that inhibitory antisense RNAs contain sequences complementary to the AUG initiation codon of the tat gene and have a comparatively low tendency to form intramolecular base pairs which would interfere with intermolecular duplex formation. Inhibition can be substantial (over 70%) but is transient. Transience does not result from mutation of the input virus. Inhibition was not a consequence of the induction of interferon by antisense RNA-mRNA duplex formation. Our results suggest that at least part of the inhibitory effect is at the posttranscriptional level.

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Section: Introductionmentioning

confidence: 99%

Inhibition of human immunodeficiency virus replication in cell culture by endogenously synthesized antisense RNA

Rhodes

James

1990

Journal of General Virology

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“…This effect is obtained by the hybridization of passive antisense molecules with their respective complementary mRNA to form nontranslatable double-stranded RNA molecules or DNA-RNA hybrids that promote the activity of endogenous RNase H, an enzyme that specifically digests the RNA strand of DNA-RNA hybrid molecules (16)(17)(18). In cultured tumor cells, antisense oligonucleotides have been shown to suppress effectively translation of several genes and to reverse some phenotypes (19)(20)(21)(22).…”

mentioning

confidence: 99%

Inhibition of HPV-16 E6/E7 immortalization of normal keratinocytes by hairpin ribozymes

Álvarez-Salas

Cullinan²,

Siwkowski

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

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HPV-16 E6 and E7 genes are required to efficiently immortalize a broad spectrum of cell types including cervical keratinocytes. Therefore, the E6͞E7 genes can be considered relevant targets for anti-cancer therapy. We produced several engineered hairpin (HP) ribozymes to specifically disrupt HPV-16 E6͞E7 mRNA. After extensive biochemical characterization, one anti-E6 HP ribozyme (R434) was selected for in vivo testing because of its superior catalytic capabilities. When expressed in cis, R434 efficiently inhibited E6 in vitro translation. Cis-expression of the HP ribozyme with HPV-16 E6͞E7 genes in normal human keratinocytes reduced the growth rate and prevented immortalization. RNA analysis by reverse transcription-PCR showed that E6͞E7 transcripts were cleaved in post-transfected cells and virtually were eliminated after long term expression. Of interest, an inactive version of the HP also was able to significantly affect the immortalizing ability of E6͞E7, probably through passive hybridization. The combination of passive and cleaving antisense RNA therefore is established as an effective inhibitor of HPV-16 E6͞E7 immortalization.Over one-half of invasive cervical carcinomas worldwide and many cervical carcinoma-derived cell lines contain and express DNA from human papillomavirus type 16 (HPV-16). In early stages, HPV-16 expression causes benign proliferation and efficiently immortalizes cultured human epithelial cells, including cervical keratinocytes (1-3). The HPV-16 viral, early genes E6 and E7 are required to acquire and maintain efficiently the transformed phenotype in a broad spectrum of cell types and commonly are expressed in cervical carcinoma cells. Thus, E6͞E7 genes are the hallmark of cervical carcinoma (4-7). The E6 and E7 proteins bind with high affinity the p53 and Rb tumor suppressors, respectively (8, 9). The interaction of HPV-16 E6 protein with p53 results in degradation through the ubiquitin pathway, resulting in the equivalent of a mutant p53 phenotype (10-12). The association of E7 with Rb impedes the interaction of Rb with several proteins (i.e., E2F), efficiently disrupting the cell cycle (13-15). Therefore, the E6͞E7 genes are ideal targets for anti-cancer therapy.Antisense RNA and oligonucleotides have been used specifically to block translation of several genes. This effect is obtained by the hybridization of passive antisense molecules with their respective complementary mRNA to form nontranslatable double-stranded RNA molecules or DNA-RNA hybrids that promote the activity of endogenous RNase H, an enzyme that specifically digests the RNA strand of DNA-RNA hybrid molecules (16)(17)(18). In cultured tumor cells, antisense oligonucleotides have been shown to suppress effectively translation of several genes and to reverse some phenotypes (19)(20)(21)(22). However, passive antisense therapy has the disadvantage of being active for a limited period and often causing nonspecific toxicity (23,24). This approach has produced inhibition of E6͞E7 gene expression in HPV-18-containin...

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“…After hybridization with activin ␤A polyclonal antibody and chemiluminescence for visualization, the correct 16-kD band (line) was not visible in the UCM and CCM from embryos identified by PCR as homozygous for the mutated activin ␤A allele (lanes -), but was found in the CCM from PCR positive sibs (lanes ϩ). H) degradation (Walder, 1988). Zamecnik and Stephenson (1978) showed that short oligonucleotides could be used in cultured cells to block gene function.…”

Section: Discussionmentioning

confidence: 99%

Expression and function of activin beta A during mouse cardiac cushion tissue formation

1998

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Antisense DNA and RNA: progress and prospects.

Cited by 64 publications

References 10 publications

Inhibition of human immunodeficiency virus replication in cell culture by endogenously synthesized antisense RNA

Inhibition of human immunodeficiency virus replication in cell culture by endogenously synthesized antisense RNA

Inhibition of HPV-16 E6/E7 immortalization of normal keratinocytes by hairpin ribozymes

Expression and function of activin beta A during mouse cardiac cushion tissue formation

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