Delivery of gene products via mesangial cells

Details Delivery of gene products via mesangial cells Delivery of gene products via mesangial cells

1993-11-17

1996-12-03

Stanton, Brian R.

Drug, bio-affecting and body treating compositions

Whole live micro-organism, cell, or virus containing

Genetically modified micro-organism, cell, or virus

424 931, 424 932, 435 691, 435 697, 435 711, 4351723, 4352402, 43524021, 935 62, 935 70, 935 71, 935 34, A61K 4800, A61K 3512, C12N 1563, C12N 506

Patent

active

055805582

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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