Binding of antisense phosphorothioate oligonucleotides to murine lymphocytes is lineage specific and inducible.

Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.

Binding of antisense phosphorothioate oligonucleotides to murine lymphocytes is lineage specific and inducible.

Antisense Res Dev. 1992 Fall;2(3):223-33. Unique Identifier : AIDSLINE MED/93144893
Iversen PL; Crouse D; Zon G; Perry G; Department of Pharmacology, University of Nebraska Medical; Center, Omaha.

Abstract: A phosphorothioate oligonucleotide that has been employed to inhibit HIV-1 viral expression in chronically infected H9 cells was examined for its ability to associate with murine lymphoid cells. The relationship between cellular oligonucleotide concentration and the lymphoid target tissues is important to the selection of an animal model, evaluation of potential side effects, and understanding the actions of a therapeutically useful antisense oligonucleotide. Lymphoid cells were harvested from murine peripheral blood, bone marrow, thymus, lymph node, and spleen. Cell subpopulations that bind the oligonucleotide were distinguished by two-color flow cytometry employing a fluorescein-labeled anti-rev oligonucleotide and phycoerythrin-labeled antibodies to selected cell surface molecules associated with unique subpopulations of cells. Very little oligonucleotide binding was observed in peripheral blood mononuclear cells or thymic T cells, but substantial numbers of cells, primarily B cells from bone marrow and spleen, accumulated the oligonucleotide. The cell-associated oligonucleotide was increased significantly in lymphoid populations when the cells were mitogen pretreated with either concanavalin-A (ConA), a T cell mitogen, or lipopolysaccharide (LPS), a B cell mitogen. These data clearly demonstrate the ability of fluorescein-conjugated oligonucleotides to bind to unique cell populations in suspension, allowing simultaneous two-color phenotypic analysis, suggesting that fluorescein-conjugated oligonucleotides may be a useful bridge between in vitro molecular biology techniques and in vivo cell biology. In addition, these data provide optimism concerning the in vivo treatment of chronically infected HIV patients using antisense oligonucleotides.

Keywords: Animal Base Sequence Binding Sites Bone Marrow/CYTOLOGY/METABOLISM Female Lymph Nodes/CYTOLOGY/METABOLISM Lymphocyte Subsets/*METABOLISM *Lymphocyte Transformation Mice Mice, Inbred Strains Molecular Sequence Data Oligonucleotides, Antisense/*METABOLISM Sensitivity and Specificity Spleen/CYTOLOGY/METABOLISM Thionucleotides/*METABOLISM Thymus Gland/CYTOLOGY/METABOLISM JOURNAL ARTICLE
930530
M9350948

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