The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.
Therapeutic EphA2 Gene Targeting In vivo Using Neutral Liposomal Small Interfering RNA Delivery
Abstract
Inducing destruction of specific mRNA using small interfering RNA (siRNA) is a powerful tool in analysis of protein function, but its use as a therapeutic modality has been limited by inefficient or impractical delivery systems. We have used siRNA incorporated into the neutral liposome 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) for efficient in vivo siRNA delivery. In nude mice bearing i.p. ovarian tumors, nonsilencing siRNA tagged with the fluorochrome Alexa 555 was encapsulated into DOPC liposomes and shown to be taken up by the tumor as well as many major organs. Furthermore, DOPC-encapsulated siRNA targeting the oncoprotein EphA2 was highly effective in reducing in vivo EphA2 expression 48 hours after a single dose as measured by both Western blot and immunohistochemistry. Therapy experiments in an orthotopic mouse model of ovarian cancer were initiated 1 week after injection of either HeyA8 or SKOV3ip1 cell lines. Three weeks of treatment with EphA2-targeting siRNA-DOPC (150 μg/kg twice weekly) reduced tumor growth when compared with a nonsilencing siRNA (SKOV3ip1: 0.35 versus 0.70 g; P = 0.020; HeyA8: 0.98 versus 1.51 g; P = 0.16). When EphA2-targeting siRNA-DOPC was combined with paclitaxel, tumor growth was dramatically reduced compared with treatment with paclitaxel and a nonsilencing siRNA (SKOV3ip1: 0.04 versus 0.22 g; P < 0.001; HeyA8: 0.21 versus 0.84 g; P = 0.0027). These studies show the feasibility of siRNA as a clinically applicable therapeutic modality.
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1 retracted
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Cited by
MicroRNA therapeutics: towards a new era for the management of cancer and other diseases
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Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma
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Self-citation
Metadata
- Authors
- Landen, C. N., Chavez-Reyes, A., Bucana, C., Schmandt, R., Deavers, M. T., Lopez-Berestein, G., & Sood, A. K.
- Venue
- Cancer Research
- Published
- 2005-08-01
- Volume
- 65
- Issue
- 15
- Pages
- 6910-6918
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2129825215
- Cited by
- 675
- References
- 52
- FWCI
- 11.52
- Type
- journal article
- Language
- en
- Open access
- closed
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- Landen, C. N., Chavez-Reyes, A., Bucana, C., Schmandt, R., Deavers, M. T., Lopez-Berestein, G., & Sood, A. K. (2005). Therapeutic EphA2 Gene Targeting In vivo Using Neutral Liposomal Small Interfering RNA Delivery. Cancer Research. https://doi.org/10.1158/0008-5472.can-05-0530
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