Conditionally replicating adenovirus to express REIC gene
AssigneesNational University Corporation Okayama University, Momotaro-Gene Inc., Industry-University Cooperation Foundation Hanyang University
InventorsHiromi Kumon, Yasutomo Nasu, Masami Watanabe, Chae Ok Yun
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Abstract
An object of the present invention is to provide a conditionally replicating adenovirus having a strong anticancer effect. A conditionally replicating adenovirus to replicate specifically in a cancer cell and express REIC protein or REIC C domain protein, wherein the conditionally replicating adenovirus is obtained by inserting full-length REIC DNA or REIC C domain DNA into a conditionally replicating adenovirus comprising an ITR (inverted terminal repeat) sequence of an adenovirus type 5 genome and insertion of an HRE sequence, an hTERT promoter, a decorin-encoding DNA, and a DNA encoding a peptide comprising an RGD sequence.
Claims6
A conditionally replicating adenovirus that replicates specifically in a cancer cell and expresses REIC protein or REIC C domain protein, comprising:
- (a) a DNA sequence encoding a REIC protein selected from the group consisting of a full-length REIC protein and a REIC C domain protein;
- (b) an ITR (inverted terminal repeat) sequence of an adenovirus type 5 genome;
- an insertion of at least one HRE sequence, an hTERT promoter, a decorin-encoding DNA, and a DNA encoding a peptide comprising an RGD sequence, wherein
- (i) the hTERT promoter is an hTERT promoter modified through addition of a c-Myc binding site and an Sp1 binding site;
- (ii) six HRE sequences each consisting of a nucleotide sequence as set forth in SEQ ID NO:
- 3 are inserted upstream of the hTERT promoter;
- (iii) an Rb binding region (Retinoblastoma gene binding region), being a part of an E1A region, in the adenovirus type 5 genome sequence as set forth in as SEQ ID NO:
- 4 is deleted;
- (iv) nucleotides of a portion encoding E1B-19 kDa, being a part of an E1B region, in the adenovirus type 5 genome sequence as set forth in as SEQ ID NO:
- 4 are deleted;
- (v) an E3 region is partially deleted;
- (vi) a DNA construct consisting of a promoter sequence, the decorin-encoding DNA, and a poly A addition sequence is inserted into the E3 region;
- (vii) the DNA encoding a peptide comprising an RGD sequence is inserted into the E3 region;
- and
- (viii) a DNA construct consisting of a CMV promoter sequence, a DNA encoding REIC DNA or REIC C domain DNA, and a poly A addition sequence is inserted into an E1 region.
Dependencies are inferred from the claim text.