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Published on: August 25, 2021
Tumor cell-specific gene expression by 5'-flanking DNA of murine Q5 gene in an adenoviral vector system
Eri Kuwada1, Katsuo Noguchi, Kenji Hasezawa
1Medinet Medical Institute, Medinet Co., Ltd., Setagaya-ku, Tokyo, Japan.
Background:
Regulatory DNA that would induce tumor cell-specific gene expression of arbitrary genes in human cells has been sought. We previously reported that the transcription of mouse Q5 gene was tumor-selective and hypothesized that Q5 5'-flanking DNA had a key role in tumor-selective transcription.
Materials And Methods:
Isolation of 3.9 kb Q5 5'-flanking DNA was carried out and the sequence characteristics determined. Reporter plasmids, recombinant reporter adenoviruses and recombinant reporter lentiviruses were prepared that contained the Q5 5'-flanking DNA fragments of various lengths. Expression of these reporter genes was examined in various murine cells in vitro and in vivo and in various human cells in vitro.
Results:
Adenovirus vectors that had Q5 5'-flanking DNA contained a regulatory region and induced tumor cell-specific gene expression not only in mouse cells but also in human cells.
Conclusion:
Our newly constructed vector system could be utilized in gene therapy of human cancer.
Insights
Researchers identified tumor-selective regulatory DNA from mouse Q5 gene flanking regions. This DNA enables tumor cell-specific gene expression in both mouse and human cells, offering potential for cancer gene therapy.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Research
Background:
- The search for regulatory DNA to drive tumor-specific gene expression in human cells is ongoing.
- Previous studies indicated tumor-selective transcription of the mouse Q5 gene.
- A hypothesis proposed that Q5 5'-flanking DNA plays a crucial role in this tumor selectivity.
Purpose of the Study:
- To isolate and characterize the Q5 5'-flanking DNA.
- To construct and test vector systems utilizing this DNA for tumor-specific gene expression.
Main Methods:
- Isolation and sequencing of 3.9 kb Q5 5'-flanking DNA.
- Construction of reporter plasmids, adenoviruses, and lentiviruses with varying lengths of Q5 5'-flanking DNA.
- In vitro and in vivo expression analysis in murine and human cells.
Main Results:
- The Q5 5'-flanking DNA contains a regulatory region.
- Adenovirus vectors incorporating this DNA demonstrated tumor cell-specific gene expression.
- This tumor selectivity was observed in both mouse and human cells.
Conclusions:
- A novel vector system utilizing Q5 5'-flanking DNA has been developed.
- This system effectively induces tumor cell-specific gene expression across species.
- The findings suggest potential applications in gene therapy for human cancers.
