A top-down approach for construction of hybrid polymer-virus gene delivery vectors

Joshua D. Ramsey, Halong N. Vu, Daniel W. Pack

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Safe and efficient delivery of therapeutic nucleic acids remains the primary hurdle for human gene therapy. While many researchers have attempted to re-engineer viruses to be suited for gene delivery, others have sought to develop non-viral alternatives. We have developed a complementary approach in which viral and synthetic components are combined to form hybrid nanoparticulate vectors. In particular, we complexed non-infectious retrovirus-like particles lacking a viral envelope protein, from Moloney murine leukemia virus (M-VLP) or human immunodeficiency virus (H-VLP), with poly-l-lysine (PLL) or polyethylenimine (PEI) over a range of polymer/VLP ratios. At appropriate stoichiometry (75-250μg polymer/106 VLP), the polymers replace the function of the viral envelope protein and interact with the target cell membrane, initiate cellular uptake and facilitate escape from endocytic vesicles. The viral particle, once in the cytosol, efficiently completes its normal infection process including integration of viral genes with the host genome as demonstrated by long-term (at least 5weeks) transgene expression. In addition, hybrid vectors comprising H-VLP were shown to be capable of infecting non-dividing cells.

Original languageEnglish
Pages (from-to)39-45
Number of pages7
JournalJournal of Controlled Release
Issue number1
StatePublished - May 2010

Bibliographical note

Funding Information:
We thank Sandy McMasters at the SCS Cell Media Facility for her advice and assistance with the cell lines used in this study and Lou Ann Miller at the UIUC Center for Microscopic Imaging for her assistance with the transmission electron microscopy. We are grateful for the financial support of the National Science Foundation ( CBET 06-02636 ).


  • Gene delivery
  • Hybrid vectors
  • Murine leukemia virus
  • Polyethylenimine
  • Polylysine

ASJC Scopus subject areas

  • Pharmaceutical Science


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