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Protein delivery using engineered virus-like particles

  1. Author:
    Kaczmarczyk, S. J.
    Sitaraman, K.
    Young, H. A.
    Hughes, S. H.
    Chatterjee, D. K.

  2. Author Address

    [Kaczmarczyk, SJ; Sitaraman, K; Chatterjee, DK] NCI, Prot Express Lab, Adv Technol Program, Sci Applicat Int Corp SAIC Frederick Inc, Frederick, MD 21702 USA. [Young, HA] NCI, Expt Immunol Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. [Hughes, SH] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA.;Chatterjee, DK (reprint author), NCI, Prot Express Lab, Adv Technol Program, Sci Applicat Int Corp SAIC Frederick Inc, Frederick, MD 21702 USA;dchatterjee@mail.nih.gov
    1. Year: 2011
    2. Date: Oct
  2. Journal: Proceedings of the National Academy of Sciences of the United States of America
    1. 108
    2. 41
    3. Pages: 16998-17003
  4. Type of Article: Article
  5. ISSN: 0027-8424
  1. Abstract:

    Over the years, researchers have developed several methods to deliver macromolecules into the cytosol and nucleus of living cells. However, there are limitations to all of these methods. The problems include (i) inefficient uptake, (ii) endosomal entrapment, (iii) delivery that is restricted to certain cell types, and (iv) damage to cells in the delivery process. Retroviral vectors are often used for gene delivery; however, integration of the genome of retroviral vector into the host genome can have serious consequences. Here we describe a safe alternative in which virus-like particles (VLPs), derived from an avian retrovirus, are used to deliver protein to cells. We show that these VLPs are a highly adaptable platform that can be used to deliver proteins either as part of Gag fusion proteins (intracellular delivery) or on the surface of VLPs. We generated VLPs that contain Gag-Cre recombinase, Gag-Fcy::Fur, and Gag-human caspase-8 as a proof-of-concept and demonstrated that the encapsidated proteins are active in recipient cells. In addition, we show that murine IFN-gamma and human TNF-related apoptosis-inducing ligand can be displayed on the surface of VLPs, and that these modified VLPs can cause the appropriate response in cells, as evidenced by phosphorylation of STAT1 and induction of cell death, respectively.

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External Sources

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  2. DOI: 10.1073/pnas.1101874108
  3. View record in Web of Science®
  4. WOS: 000295973800030

Library Notes

  1. Fiscal Year: FY2011-2012
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