Efficient transfer of genes into murine cardiac grafts by Starburst polyamidoamine dendrimers.

TitleEfficient transfer of genes into murine cardiac grafts by Starburst polyamidoamine dendrimers.
Publication TypeJournal Article
Year of Publication1998
AuthorsQin L, Pahud DR, Ding Y, Bielinska AU, Kukowska-Latallo JF, Baker JR, Bromberg JS
JournalHum Gene Ther
Date Published1998 Mar 01
KeywordsAnimals, beta-Galactosidase, Dendrimers, Ear, External, Gene Expression, Gene Transfer Techniques, Genetic Vectors, Graft Survival, Heart Transplantation, Immunosuppressive Agents, Interleukin-10, Mice, Mice, Inbred Strains, Myocardium, Plasmids, Polyamines, Recombinant Fusion Proteins, Transplantation, Heterotopic

Starburst dendrimer, a structurally defined, spherical macromolecule composed of repeating polyamidoamino subunits, was investigated to augment plasmid-mediated gene transfer efficiency in a murine cardiac transplantation model. The grafts were directly injected with naked pCH110, a plasmid encoding beta-galactosidase (beta-Gal), or pCH110-dendrimer complex, and reporter gene expression determined by X-Gal staining. The grafts injected with pCH110-dendrimer demonstrated widespread and extended beta-Gal expression in both myocytes and the graft infiltrating cells from 7 to 28 days, compared to the grafts injected with naked pCH110 that expressed beta-Gal only in myocytes for less than 14 days. p alphaMHC-vIL-10, as plasmid encoding viral interleukin-10 (vIL-10) under the control of alpha-myosin heavy chain promoter, was able to prolong allograft survival from 13.9 +/- 0.9 days to 21.4 +/- 2.3 days (p < 0.005). When dendrimer G5EDA was used with p alphaMHC-vIL-10, 60-fold less DNA resulted in significant prolongation of graft survival to 38.6 +/- 4.7 days (p < 0.0005). The dose of DNA, the charge ratio of DNA to dendrimer, and the size generation of the dendrimers were all determined to be critical variables for prolongation of allograft survival in this model system. Thus, the use of the Starburst dendrimer dramatically increased the efficiency of plasmid-mediated gene transfer and expression. Production of immunosuppressive cytokines at higher amounts for longer periods of time in a greater expanse of tissue enhanced the immunosuppressive effect and prolonged graft survival further.

Alternate JournalHum Gene Ther
PubMed ID9525316
Grant ListP60-AR20557 / AR / NIAMS NIH HHS / United States
Related Faculty: 
Lihui Qin, M.D., Ph.D.

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