| 摘要 |
PCT No. PCT/US95/05595 Sec. 371 Date Jan. 15, 1997 Sec. 102(e) Date Jan. 15, 1997 PCT Filed May 4, 1995 PCT Pub. No. WO95/30762 PCT Pub. Date Nov. 16, 1995The invention relates to DNA constructs comprising an exogenous DNA sequence encoding a therapeutic protein product or itself a therapeutic product, DNA sequences derived from SV40 for replication and packaging of said construct into pseudovirions, and a DNA sequence encoding one or more regulatory elements sufficient for the expression of said therapeutic protein in a mammalian cell operatively linked thereto. The therapeutic product integrated into the DNA constructs of the invention can be a protein selected from the group consisting of enzymes, receptors, structural proteins, regulatory proteins and hormones. Of particular interest are beta -globin, P-glycoprotein and apolipoprotein A-I. Specific DNA constructs are plasmids pSO6 beta -9, pSO6 beta -1, pSO41, pSM1, and pSAIc. The invention also relates to SV40 pseudovirions containing a DNA construct according to the invention, which are capable of infecting and being expressed in mammalian cells. Also within the scope of the invention are transduced mammalian cells having integrated into their genome a DNA construct according to the invention, said cells being capable of expressing the therapeutic protein product. The invention also relates to a method for in vivo and ex vivo treatment of an individual suffering from an acquired or hereditary pathological disorder, in which a therapeutic product is not made by said individual, or is made in abnormally low amounts or in a defective form or is normally made in physiological amounts to be increased by employing the DNA construct, pseudovirions or transduced cells of the invention. |
