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Showing papers by "Philipp Hadwiger published in 2003"


Journal ArticleDOI
15 Apr 2003-Blood
TL;DR: SiRNAs are promising tools for a functional analysis of AML1/MTG8 and may be used in a molecularly defined therapeutic approach for t(8;21)-positive leukemia.

177 citations


Patent
07 Mar 2003
TL;DR: In this article, a double-stranded ribonucleic acid (dsRNA) having a nucleotide sequence which is substantially identical to at least a part of a target gene and which is no more than 49, preferably less than 25, nucleotides in length, and which comprises a complementary (antisense) RNA strand having a 1 to 4 nucleotide overhang at the 3′ end and a blunt 5′-end.
Abstract: The present invention relates to a double-stranded ribonucleic acid (dsRNA) having a nucleotide sequence which is substantially identical to at least a part of a target gene and which is no more than 49, preferably less than 25, nucleotides in length, and which comprises a complementary (antisense) RNA strand having a 1 to 4 nucleotide overhang at the 3′-end and a blunt 5′-end. The invention further relates to a pharmaceutical composition comprising the dsRNA and a pharmaceutically acceptable carrier. The pharmaceutical compositions are useful for inhibiting the expression of a target gene, as well as for treating diseases caused by expression of the target gene, at low dosages (i.e., less than 5 milligrams, preferably less than 25 micrograms, per kg body weight per day). The invention also relates to methods for inhibiting the expression of a target gene, as well as methods for treating diseases caused by the expression of the gene.

119 citations


Journal ArticleDOI
TL;DR: A key role for Bcl-2 in conferring chemoresistance to melanoma is underline and Bcl2 siRNA strategies are highlighted as novel and highly effective tools, with the potential for future targeted therapy of malignant melanoma.
Abstract: Malignant melanoma is a prime example of a treatment-resistant tumor with poor prognosis. Even with innovative treatment regimens, response rates remain low, and the duration of responses is short....

84 citations


Patent
11 Aug 2003
TL;DR: In this paper, a double-stranded oligoribonucleic acid (dsRNA) having a nucleotide sequence substantially identical to at least a part of a target gene in a mammalian cell and which is less than 25 nucleotides in length, together with a pharmaceutically acceptable carrier is presented.
Abstract: The present invention relates to pharmaceutical compositions comprising a double-stranded oligoribonucleic acid (dsRNA) having a nucleotide sequence which is substantially identical to at least a part of a target gene in a mammalian cell and which is less than 25 nucleotides in length, together with a pharmaceutically acceptable carrier. The pharmaceutical compositions are useful for inhibiting the expression of a target gene, as well as for treating diseases caused by expression of the target gene, in a mammal at very low dosages (i.e., less than 5 milligrams, preferably less than 25 micrograms, per kg body weight per day). The invention also relates to methods for inhibiting the expression of a target gene in a mammal, as well as methods for treating diseases caused by expression of the gene.

34 citations


Journal ArticleDOI
TL;DR: Fluorescein-labeled siRNAs may lead to false negative results and should not be used to examine electroporation-mediated siRNA uptake, and Cy3 and Cy5- labels cause a significant amount of cell fluorescence, as judged by flow cytometry.
Abstract: Transfection of mammalian cells with preformed small interfering RNAs (siRNAs) permits a transient and often specific reduction of gene expression. It is possible to rapidly examine the uptake of siRNAs by transfection with fluorescently labeled siRNAs. We examined the apparent uptake of such siRNAs by several leukemic cell lines after electroporation. We show that Cy3 and Cy5-labeled siRNAs cause a significant amount of cell fluorescence, as judged by flow cytometry. In contrast, several fluorescein-labeled siRNAs could not be detected. Nevertheless, such fluoresceinated siRNAs efficiently suppressed a leukemic target gene, demonstrating that siRNA uptake must have taken place. Therefore, for cell electroporation, fluorescein-labeled siRNAs may lead to false negative results and should not be used to examine electroporation-mediated siRNA uptake.

28 citations


Journal ArticleDOI
01 May 2003
TL;DR: This unit provides information how to use short interfering RNA for sequence specific gene silencing in mammalian cells by several ways for siRNA generation and optimisation, as well as recommendations for cell transfection.
Abstract: This unit provides information how to use short interfering RNA (siRNA) for sequence-specific gene silencing in mammalian cells. Several methods for siRNA generation and optimization, as well as recommendations for cell transfection and transduction, are presented. © 2015 by John Wiley & Sons, Inc. Keywords: RNA interference; siRNA; shRNA; transfection; electroporation; lentiviral transduction

6 citations


Journal ArticleDOI

2 citations