Delivery of gene products via mesangial cells

Drug – bio-affecting and body treating compositions – Whole live micro-organism – cell – or virus containing

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424 932, 424 9321, 435 691, 435 697, 435 711, 4351723, 935 62, 935 70, 935 71, A61K 4800, A61K 3112, C12N 506, C12N 1563

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active

056677774

ABSTRACT:
Disclosed are methods that achieve i) site-directed delivery, ii) in situ amplification, and iii) sustained expression of an exogenous gene product within renal glomeruli. An exogenous gene, E. coli .beta.-galactosidase, was introduced into cultured rat mesangial cells using a replication-defective retrovirus, and stable infectants were administered to a rat kidney via the renal artery. In the injected kidney, the engineered, cultured mesangial cells populated 40% of glomeruli site-specifically. The gene product was detected throughout a 14-week period of observation. In an alternative method, engineered, cultured mesangial cells were injected into a kidney subjected to an antibody that induces mesangiolysis followed by mesangial regeneration. Under these conditions, expression of .beta.-galactosidase was dramatically amplified in situ, and high level expression continued for at least 8 weeks.

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