Intracellular neutralization of a virus using a cell-penetrating molecular transporter

Nanomedicine (Lond). 2014 Aug;9(11):1613-24. doi: 10.2217/nnm.13.139. Epub 2013 Nov 6.

Abstract

Aims: Antibodies are the principal mediator of immunity against reinfection with viruses. Antibodies typically neutralize viruses by binding to virion particles in solution prior to attachment to susceptible cells. Once viruses enter cells, conventional antibodies cannot inhibit virus infection or replication. It is desirable to develop an efficient and nontoxic method for the introduction of virus-inhibiting antibodies into cells.

Materials & methods: In this article, we report a new method for the delivery of small recombinant antibody fragments into virus-infected cells using a dendrimer-based molecular transporter.

Results & conclusion: The construct penetrated virus-infected cells efficiently and inhibited virus replication. This method provides a novel approach for the immediate delivery of inhibitory antibodies directed to virus proteins that are exposed only in the intracellular environment. This approach circumvents the current and rather complicated expression of inhibitory antibodies in cells following gene transfer.

Keywords: antiviral agents; dendrimers; intracellular neutralization; molecular transporter; rotavirus.

MeSH terms

  • Animals
  • Antibodies / chemistry*
  • Antibodies, Monoclonal / chemistry
  • Biological Transport
  • Capsid Proteins / chemistry
  • Cytoplasm / metabolism
  • Dendrimers / chemistry
  • Enzyme-Linked Immunosorbent Assay
  • Gene Transfer Techniques
  • HIV-1 / immunology
  • Humans
  • Immunoglobulin Fragments / chemistry
  • Kidney
  • Macaca mulatta
  • Magnetic Resonance Spectroscopy
  • Microscopy, Confocal
  • Nanomedicine / methods*
  • Neutralization Tests
  • Peptides / chemistry
  • RNA, Small Interfering / metabolism
  • Rotavirus / metabolism
  • Virion / chemistry*
  • Viruses / chemistry

Substances

  • Antibodies
  • Antibodies, Monoclonal
  • Capsid Proteins
  • Dendrimers
  • Immunoglobulin Fragments
  • Peptides
  • RNA, Small Interfering