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Specific targeting of antisense olig...

Mirochnik, Yelena.

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Specific targeting of antisense oligodeoxynucleotides to prostate tumors by antibody-derived delivery vehicles.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Specific targeting of antisense oligodeoxynucleotides to prostate tumors by antibody-derived delivery vehicles./
Author:	Mirochnik, Yelena.
Description:	101 p.
Notes:	Source: Dissertation Abstracts International, Volume: 64-01, Section: B, page: 0150.
Contained By:	Dissertation Abstracts International64-01B.
Subject:	Biology, Cell. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3078906
ISBN:	0493999876

Specific targeting of antisense oligodeoxynucleotides to prostate tumors by antibody-derived delivery vehicles.
Mirochnik, Yelena.

Specific targeting of antisense oligodeoxynucleotides to prostate tumors by antibody-derived delivery vehicles. - 101 p.

Source: Dissertation Abstracts International, Volume: 64-01, Section: B, page: 0150.

Thesis (Ph.D.)--Rush University, 2003.

Antibodies specific for prostate tumor-associated antigens offer great potentials for targeting antisense oligodeoxynucleotides (ODNs) to prostate cancers. In this study we evaluated the delivery system consisting of antibody-derived delivery vehicles (DVs) recognizing prostate specific antigen (PSA) or prostate specific membrane antigen (PSMA), and synthetic biotinylated ODN targeting mRNA encoding epidermal growth factor receptor (EGFR). Two types of delivery vehicles were generated by modification of mouse monoclonal antibodies: (1) bispecific heteroconjugate antibody recognizing both PSA and biotin (DVHc); and (2) avid in-conjugated antibody specific for PSA or PSMA (DV PSA, DVPSMA). The immunoreactivity of these delivery vehicles, their ability to form complexes with biotinylated ODNs and the cellular uptake of the complexes into human prostatic carcinoma cells (LNCaP) were tested <italic> in vitro</italic>. Although both modifications produced DVs able to direct ODNs to prostate tissue <italic>in vitro</italic>, the avidin conjugates were more efficient and stable, and were further analyzed <italic>in vivo</italic>.

ISBN: 0493999876Subjects--Topical Terms:

1017686
Biology, Cell.

Specific targeting of antisense oligodeoxynucleotides to prostate tumors by antibody-derived delivery vehicles.
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100 1 $a Mirochnik, Yelena. $3 1942988
245 1 0 $a Specific targeting of antisense oligodeoxynucleotides to prostate tumors by antibody-derived delivery vehicles.
300 $a 101 p.
500 $a Source: Dissertation Abstracts International, Volume: 64-01, Section: B, page: 0150.
500 $a Director: Marvin Rubenstein.
502 $a Thesis (Ph.D.)--Rush University, 2003.
520 $a Antibodies specific for prostate tumor-associated antigens offer great potentials for targeting antisense oligodeoxynucleotides (ODNs) to prostate cancers. In this study we evaluated the delivery system consisting of antibody-derived delivery vehicles (DVs) recognizing prostate specific antigen (PSA) or prostate specific membrane antigen (PSMA), and synthetic biotinylated ODN targeting mRNA encoding epidermal growth factor receptor (EGFR). Two types of delivery vehicles were generated by modification of mouse monoclonal antibodies: (1) bispecific heteroconjugate antibody recognizing both PSA and biotin (DVHc); and (2) avid in-conjugated antibody specific for PSA or PSMA (DV PSA, DVPSMA). The immunoreactivity of these delivery vehicles, their ability to form complexes with biotinylated ODNs and the cellular uptake of the complexes into human prostatic carcinoma cells (LNCaP) were tested <italic> in vitro</italic>. Although both modifications produced DVs able to direct ODNs to prostate tissue <italic>in vitro</italic>, the avidin conjugates were more efficient and stable, and were further analyzed <italic>in vivo</italic>.
520 $a The distribution of radioactive ODN-DV complexes in tissues of athymic nude mice bearing LNCaP tumors demonstrated significant increases in cumulative tissue retention of ODNs targeted by prostate-specific DVs (DVPSA and DVPSMA). The increases were mainly due to accumulation in metabolic organs such as liver and spleen, however no differences were found in tumors.
520 $a In addition we examined the effect of EGFR specific ODNs on the proliferation of LNCaP cells. Although <super>3</super>H-thymidine incorporation demonstrated growth inhibition, ELISA and real time PCR indicated no changes in protein expression between scrambled controls and EGFR specific ODNs. The sequence analysis of ODNs employed in this study revealed a high content of contiguous guanosine residues.
520 $a We conclude that although avidin-modified DVs provide more stable ODN-DV complexes in vitro, the efficiency of this delivery system <italic>in vivo </italic> is complicated by high molecular weight of the complexes, heterogeneity of the prostate tumor, and antibody metabolism. Our study also suggests that inhibitory effect of EGFR ODNs on LNCaP cell proliferation might be a result of sequence-specific, but not “antisense-specific” mechanisms.
520 $a Future studies should concentrate on improvements in the design of DVs, as well as administration strategies to overcome problems associated with <italic> in vivo</italic> metabolism of antibody-derived delivery vehicles.
590 $a School code: 0821.
650 4 $a Biology, Cell. $3 1017686
650 4 $a Health Sciences, Oncology. $3 1018566
650 4 $a Biology, Molecular. $3 1017719
690 $a 0379
690 $a 0992
690 $a 0307
710 2 0 $a Rush University. $3 1261752
773 0 $t Dissertation Abstracts International $g 64-01B.
790 1 0 $a Rubenstein, Marvin, $e advisor
790 $a 0821
791 $a Ph.D.
792 $a 2003
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3078906