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Related Experiment Videos

(Patho)physiologic pathways to drug targeting: artificial viral envelopes

H Schreier1, M Ausborn, S Günther

  • 1Center for Lung Research, Vanderbilt University, School of Medicine, Nashville, Tennessee 37232-2650, USA.

Journal of Molecular Recognition : JMR
|January 1, 1995
PubMed
Summary

Researchers created artificial viral envelopes (AVE) to deliver large molecules into cells. These envelopes mimic HIV-1 and target CD4 receptors, successfully delivering macromolecules like FITC-dextran and ricin A into specific cells.

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Area of Science:

  • Biotechnology
  • Molecular Biology
  • Drug Delivery Systems

Background:

  • Cell surface receptors mediate molecular recognition.
  • Viral surface glycoproteins can target specific cell receptors.
  • Intracellular delivery of macromolecules is challenging due to cell membrane barriers.

Purpose of the Study:

  • To develop artificial viral envelopes (AVE) for targeted intracellular delivery of macromolecules.
  • To utilize molecular recognition between viral glycoproteins and cell surface receptors for selective delivery.
  • To demonstrate the efficacy of AVE in delivering non-diffusive macromolecules into specific cell types.

Main Methods:

  • Designed artificial viral envelopes (AVE) mimicking the human immunodeficiency virus-1 (HIV-1).

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  • Inserted recombinant HIV-1 surface glycoprotein gp160 into AVE using detergent dialysis.
  • Utilized FITC-dextran and ricin A as model macromolecules for delivery studies.
  • Tested AVE targeting specificity using CD4-positive and CD4-negative cell lines.

    • Main Results:

    • HIV-1 rgp160-inserted AVE selectively delivered FITC-dextran into CD4-positive cells (REX-1B) but not CD4-negative cells (KG-1).
    • Ricin A delivered via AVE arrested growth in CD4-positive MOLT-4 cells at low concentrations (2 ng/ml).
    • Growth arrest was reversible with anti-gp120 antibody, confirming specificity.
    • Naked AVE showed less efficient and non-specific material transfer.

    Conclusions:

    • Artificial viral envelopes (AVE) can mimic viral targeting mechanisms for selective intracellular delivery.
    • This viral mimicry approach shows potential for delivering various macromolecules, including peptides, proteins, and gene constructs.
    • AVE offer a promising strategy for targeted delivery of labile or toxic macromolecules into specific cells.