Deoxyribonuclease II is a lysosomal barriers to transfection

Dasein Pinto-González Howell, Ronald J. Krieser, Alan Eastman, Michael A. Barry

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

DNA delivered in nonviral vectors or as naked DNA must overcome a number of extracellular and intracellular barriers to transfection. Since many vectors deliver DNA into cells by the endocytic route, DNA degradation by lysosomal nucleases has been proposed as a significant barrier to transfection, despite the fact that this has not yet been formally demonstrated to occur. To test this hypothesis, we have investigated the role of deoxyribonuclease II (DNase II), the primary acidic endonuclease active in the lysosome, in transfection. Two genetic systems were engineered in which mammalian cells either overexpressed DNase II or were knocked out for the enzyme. In both models, higher levels of DNase II correlated with decreased transfection efficiency by nonviral DNA delivery vectors. These data provide direct evidence implicating lysosomal DNase II as a barrier to transfection.

Original languageEnglish (US)
Pages (from-to)957-963
Number of pages7
JournalMolecular Therapy
Volume8
Issue number6
DOIs
StatePublished - Dec 2003

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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