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(Patho)physiologic pathways to drug targeting: Artificial viral envelopes
Author(s) -
Schreier Hans,
Ausborn Michael,
Günther Susanne,
Weissig Volkmar,
Chander Ramesh
Publication year - 1995
Publication title -
journal of molecular recognition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.401
H-Index - 79
eISSN - 1099-1352
pISSN - 0952-3499
DOI - 10.1002/jmr.300080110
Subject(s) - viral envelope , intracellular , microbiology and biotechnology , glycoprotein , ricin , biology , monoclonal antibody , cell , cell surface receptor , receptor , cell culture , cell membrane , endocytosis , biochemistry , antibody , immunology , toxin , genetics
The goal of this study was to exploit molecular recognition of cell surface receptors by viral surface glycoproteins as a means for the selective intracellular delivery of macromolecules. To accomplish this, artificial viral envelopes (AVE) resembling the human immunodeficiency virus‐1 (HIV‐1) were designed as a model system. Recombinant HIV‐1 surface glycoprotein gp160 (HIV‐1 rgp 160) was inserted in the artificial envelope by a two‐step detergent dialysis process. The artificial HIV‐1 envelope recognized the CD4 cell surface receptor. FITC‐dextran and ricin A were employed as model macromolecules as they cannot passively diffuse across cell membranes. Selective transfer of FITC‐dextran encapsulated in HIV‐1 rgp160 AVE into a CD4‐positive cell line (REX‐1B) versus a CD4‐negative cell line (KG‐1) was demonstrated. Ricin A at concentrations as low as 2 ng/ml arrested cell growth of CD4‐positive MOLT‐4 cells, whereas 8ng/ml ricin A in solution had no effect on cell growth. The arrest of cell growth was reverted in the presence of excess anti‐gp120 monoclonal antibody. Naked enveloped (without HIV‐1 rgp 160 inserted) were alsofound to interact with cells and transfer material, although less efficiently and in a non‐specific manner. Viral mimicry using AVE may be a means for targeted intracellular delivery of peptides, proteins, enzymes, toxins, oligodeoxynucleotides, gene constructs, and other non‐diffusive, labile or toxic macromolecules.