Patterns of cellular uptake and effects on cell survival using antimetallothionein oligodeoxyribonucleotide conjugates in vitro

J. K. DiBaise, M. Ebadi, P. L. Iversen

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Synthetic oligodeoxyribonucleotides (ODNs) offer the potential for the sequence-specific modulation of viral and cellular gene expression. However, several problems such as efficient delivery into cells, metabolic stability and delivery to specific cellular targets may limit their usefulness. Studies were designed to demonstrate that the covalent conjugation of an 18 mer ODN complementary in sequence to mRNA ODN with various polypeptide ligands, including poly(L-lysine), phosphomannan and asialo-orosomucoid, elicits a pattern of enhanced yet differential uptake into Chang and V79 cells in culture. Viability of cells exposed to conjugated ODNs was measured using a colorimetric assay (MTT). The ODNs covalently linked to poly(L-lysine) reveal an increased efficiency of antisense-directed cell killing from concentrations greater than 3 μM to less than 100 nM. Finally, poly(L-lysine) is also cytotoxic, particularly at extremes of molecular weight. Hence, these studies indicate that synthetic ODNs conjugated to peptides may offer enhanced cellular uptake leading to more efficient antisense activity. However, the cytotoxicity of ODN conjugates may limit their usefulness as research tools or therapeutic agents.

Original languageEnglish (US)
Pages (from-to)140-149
Number of pages10
JournalBiological Signals
Volume3
Issue number3
StatePublished - 1994
Externally publishedYes

Fingerprint

Oligodeoxyribonucleotides
Cell Survival
Cells
Lysine
Peptides
Viral Genes
Cytotoxicity
In Vitro Techniques
Cell culture
Gene expression
Assays
Cell Culture Techniques
Molecular Weight
Molecular weight
Modulation
Ligands
Gene Expression
Messenger RNA
Research

Keywords

  • antisense oligonucleotide
  • Chang liver cells
  • metallothionein
  • phosphorothiotate oligonucleotide
  • V79 cells

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Patterns of cellular uptake and effects on cell survival using antimetallothionein oligodeoxyribonucleotide conjugates in vitro. / DiBaise, J. K.; Ebadi, M.; Iversen, P. L.

In: Biological Signals, Vol. 3, No. 3, 1994, p. 140-149.

Research output: Contribution to journalArticle

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