Bilamellar cationic liposomes protect adenovectors from preexisting humoral immune responses

Patricia Yotnda, Dong Hua Chen, Wah Chiu, Pedro A. Piedra, Alan Davis, Nancy Smyth Templeton, Malcolm Brenner

Research output: Contribution to journalArticle

99 Scopus citations

Abstract

Adenoviral vectors have been widely used for gene therapy, but they are limited both by the presence of a humoral immune response that dramatically decreases the level of transduction after reinjection and by their requirement for target cells to express appropriate receptors such as Coxsackie adenovirus receptor (CAR). To overcome both limits, we encapsulated adenovectors using bilamellar DOTAP:chol liposomes. Electron micrography (EM) showed that these liposomes efficiently encapsulated the vectors, allowing CAR-independent adenovector transduction of otherwise resistant cells. DOTAP:chol-encapsulated adenovectors encoding LacZ or α1-antitrypsin inhibitor (AAT) were also functionally resistant ex vivo and in vivo to the neutralizing effects of human anti-adenoviral antibodies, unlike other liposomal systems. Hence, bilamellar DOTAP: chol liposomes may be useful for applications using adenovectors in which the target cells lack adenoviral receptors or in which the recipient already has or develops a neutralizing antibody response that would otherwise inactivate readministered vector.

Original languageEnglish (US)
Pages (from-to)233-241
Number of pages9
JournalMolecular Therapy
Volume5
Issue number3
DOIs
StatePublished - 2002

Keywords

  • Adenovirus
  • DOTAP:chol
  • Encapsulation
  • Gene therapy
  • Lung
  • Readministration

ASJC Scopus subject areas

  • Molecular Biology

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