The Correction, in vitro, of Lysosomal Enzyme Deficiencies by Means of Immunoglobulin-Coated Liposomes
In 1965, we described, with A. D. Bangham (1) the formation of artificial lipid structures which could serve as models for the membranes of cells and/or organelles. By 1968 (2), we had coined the term “liposome” to describe these artificial, multilamellar structures, which, in their response to steroids, lytic proteins, polyene antibiotics, etc. closely resembled natural biomembranes. (The term “liposome” has now been generally accepted). Yet it was not until 1970 (3) that it became possible to encapsulate an enzyme, rather than low molecular weight solutes such as ions, glucose or dyes, into the aqueous interstices between the multilamellar lipid bilayers of liposomes. We utilized the enzyme lysozyme and established its mode of trapping in the following fashion: Gel filtration resolved liposomes formed in the absence of enzyme from free enzyme when both were chromatographed immediately after mixing. In contrast, if liposomes were permitted to form in the presence of lysozyme, subsequent chromatography disclosed two peaks of enzyme activity: one associated with liposomes, the other emerging as free lysozyme. The activity of lysozyme associated with liposomes was “latent” i.e. there was little or no activity on substrate unless the liposomes were disrupted by Triton X-100, amphotericin B, or nystatin.
KeywordsEnzyme Replacement Therapy Lysosomal Enzyme Polymorphonuclear Leukocyte Free Enzyme Enzyme Release
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