TY - JOUR
T1 - Cancer gene therapy using plasmid DNA
T2 - Pharmacokinetic study of DNA following injection in mice
AU - Lew, D.
AU - Parker, S. E.
AU - Latimer, T.
AU - Abai, A. M.
AU - Kuwahara-Rundell, A.
AU - Doh, S. G.
AU - Yang, Z. Y.
AU - Laface, D.
AU - Gromkowski, S. H.
AU - Nabel, G. J.
AU - Manthorpe, M.
AU - Norman, J.
PY - 1995
Y1 - 1995
N2 - The fate of plasmid DNA complexed with cationic lipids delivered intravenously in mice was evaluated at selected timepoints up to 6 months postinjection. Blood half-life and tissue distribution of plasmid DNA and potential expression in tissues were examined. Southern blot analyses of blood indicated that intact plasmid DNA was rapidly degraded, with a half-life of less than 5 min for intact plasmid, and was no longer detectable at 1 hr postinjection. Southern analyses of tissue demonstrated that intact DNA was differentially retained in the lung, spleen, liver, heart, kidney, marrow, and muscle up to 24 hr postinjection. After 7 days, no intact plasmid DNA was detectable by Southern blot analysis; however, the plasmid was detectable by the polymerase chain reaction (PCR) in all tissues examined at 7 and 28 days postinjection. At 6 months postinjection, femtogram levels of plasmid were detected only in muscle. Immunohistochemical analyses did not detect encoded protein in the tissues harboring residual plasmid at 1 or 7 days postinjection.
AB - The fate of plasmid DNA complexed with cationic lipids delivered intravenously in mice was evaluated at selected timepoints up to 6 months postinjection. Blood half-life and tissue distribution of plasmid DNA and potential expression in tissues were examined. Southern blot analyses of blood indicated that intact plasmid DNA was rapidly degraded, with a half-life of less than 5 min for intact plasmid, and was no longer detectable at 1 hr postinjection. Southern analyses of tissue demonstrated that intact DNA was differentially retained in the lung, spleen, liver, heart, kidney, marrow, and muscle up to 24 hr postinjection. After 7 days, no intact plasmid DNA was detectable by Southern blot analysis; however, the plasmid was detectable by the polymerase chain reaction (PCR) in all tissues examined at 7 and 28 days postinjection. At 6 months postinjection, femtogram levels of plasmid were detected only in muscle. Immunohistochemical analyses did not detect encoded protein in the tissues harboring residual plasmid at 1 or 7 days postinjection.
UR - http://www.scopus.com/inward/record.url?scp=0029099729&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029099729&partnerID=8YFLogxK
M3 - Article
C2 - 7578393
AN - SCOPUS:0029099729
SN - 1043-0342
VL - 6
SP - 553
EP - 564
JO - Human Gene Therapy
JF - Human Gene Therapy
IS - 5
ER -