Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Liposomes
Patent
1997-05-21
2000-05-09
Guzo, David
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Liposomes
514 44, 536 231, 435458, A61K 927, A61K 9133, A61K 317088
Patent
active
060600810
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to gene-containing compositions, and more particularly to gene-containing compositions for introducing a gene into fetuses carried by its pregnant mother to express the gene. The invention also relates to a method for introducing a gene into fetuses including those of experimental animals, cattle, and industrial animals.
BACKGROUND ART
In recent years, several methods have been developed for directly introducing foreign genes into animal or human bodies in the hope of applying them to gene therapy for treating diseases caused by genomic abnormalities.
Diseases caused by congenital gene abnormalities such as congenital gene deficiency are preferably treated in the prenatal stage. As regards introduction of genes into prenatal subjects, microinjection into fertilized egg in animal experiments is the sole method that is currently available [Palmitter, R. D. & Brinster, R. L.: Annu. Rev. Genet., 20, 465-499 (1986)].
Although the microinjection method applied to fertilized egg opened the way for introduction of genes into early embryogenic stage, means for introducing foreign genes into fetuses has not yet been developed. Moreover, microinjection method cannot be applied to gene therapy of fetuses in the case of human pregnancy.
Accordingly, an object of the present invention is to develop a method for introducing foreign genes into fetuses in a developmental stage, and another object of the invention is to provide a gene-containing composition for use in such a method.
DISCLOSURE OF THE INVENTION
The present inventors conducted diverse studies of means for administering intended genes to fetuses through its mother's body, and as a result, found that when genes are administered to a mother along with a specific transporter, they can pass through the placental basement membrane serving as a blood barrier between the fetuses and its mother body, and that gene can be introduced into fetal cells to express themselves in situ, leading to completion of the invention.
Accordingly, the present invention provides a gene-containing composition comprising a gene and a transporter, the transporter being capable of transporting the gene from a pregnant body to fetal cells.
The present invention also provides a method for introducing genes to fetal cells by administering the above gene-containing composition to a pregnant body.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows the results of Southern blot analysis of genomic DNA of a fetus and the maternal liver after administration of the composition of the present invention.
FIG. 2 shows the results of Southern blot analysis of genomic DNA of a fetus and the maternal liver after administration of a foreign gene alone.
FIG. 3 shows the results of Southern blot analysis of genomic DNA of a fetus when the composition is administered at days 3, 6, 9, 12, and 15 postcoitus.
FIG. 4 shows the results of Southern blot analysis of genomic DNA extracted from a mouse fetus, a newborn mouse, and a one month-old young mouse when the composition of the present invention was administered to their mothers' bodies at day 9 postcoitus.
FIG. 5 shows the results of Slot blot analysis of genomic DNA extracted from organs of the one month-old young mouse shown in FIG. 4.
FIG. 6 shows the results of Northern blot analysis of RNA extracted from a mouse fetus and a newborn mouse when the composition of the present invention was administered to their mothers' bodies at day 9 postcoitus.
FIG. 7 shows CAT activity of the proteins extracted from a mouse and a newborn mouse to which SV40-CAT gene has been introduced.
FIG. 8 (parts a-f) shows histchemical profiles obtained by staining, with X-gal, expression of .beta.-actin-lacZ which has been introduced into fetuses by administering the composition of the present invention to their mothers at day 8.5 postcoitus.
FIG. 9 (parts g-k) shows tissue slices of mouse fetuses in which .beta.-actin-lacZ which has been introduced is expressed.
FIG. 10 is a graph showing numbers of platelets of a two week-old mo
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Ochiya Takahiro
Sugimura Takashi
Terada Masaaki
Tsukamoto Makoto
Yoshida Sho
Daiichi Pharmaceutical Co. Ltd.
Guzo David
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