Genecraft, Inc.

Suk Chul Bae

You Soub Lee

Xinzi Chi

Jung Won Lee

Woo-jin Kim

Ja Yeol Lee

Tae Geun Park

Seo Yeong Yoo

The present invention relates to a pharmaceutical composition for prevention or treatment of cancer, comprising a Runx3 (Runt-related transcription factor 3) protein, a polynucleotide encoding thereof, a vector carrying the polynucleotide or a virus or cell transformed with the vector; and a CDK4 inhibitor or an mTOR inhibitor as an active ingredient. It was confirmed that the binding of Runx3 and BRD2 was maintained for up to 8 hours when the CDK4 inhibitor (PD0332991) was present at the concentration of 11 nM known to be non-toxic to normal cells. It was also confirmed that the binding of Runx3 and BRD2 was maintained for up to 8 hours when the mTOR inhibitor (rapamycin) was present at the concentration of 100 nM known to be non-cytotoxic to normal cells. In addition, it was confirmed that the cancer apoptotic effect was significantly increased when the CDK4 inhibitor or mTOR inhibitor was administered simultaneously with Runx3 than when Runx3 was administered alone to Runx3 deficient cancer cells. Therefore, the CDK4 inhibitor or mTOR inhibitor can be effectively used for preventing or treating various cancers by administering the same in combination with Runx3.

Pharmaceutical composition comprising RUNX3 protein and CDK4 inhibitor or mTOR inhibitor cotreatment for prevention or treatment of cancer

Described herein is a nucleic acid molecule including an asymmetrically modified inverted terminal repeat (ITR). An AAV vector including the nucleic acid molecule has advantages of increased productivity and expression efficiency of a transgene, and decreased genotoxicity, by having an asymmetric ITR in which any one of two ITRs is modified. Also, described herein is are compositions and vectors.

Nucleic acid molecule comprising asymmetrically modified ITR for improving expression rate of inserted gene, and use thereof

In the present invention, it was confirmed that the modified protein in which the 356serine of Runx3 is substituted with alanine has an increased activity of maintaining the complex with Brd2 by more than 10 times compared to the wild-type Runx3, and the apoptosis effect is improved in various cancer cell lines compared to the wild-type Runx3. Therefore, the modified protein in which the 356serine of Runx3 is substituted with an amino acid that cannot be phosphorylated by a kinase of the present invention, the polynucleotide coding thereof, the vector carrying the polynucleotide, or the virus or cell transformed with the vector can be used as a therapeutic agent for various cancers.

Runx3 modified protein for prevention or treatment of cancer

Described herein is an adeno-associated virus (AAV) complex platform including an asymmetrically modified inverted terminal repeat (ITR). The AAV complex has advantages of increased productivity and expression efficiency of a transgene, and decreased genotoxicity, by having an asymmetric ITR in which any one of two ITRs is modified. Also, described herein is a composition comprising the adeno-associated virus complex and a method of gene therapy.

Modified complex platform of adeno-associated virus with improved rate of expression of loaded genes and reduced genotoxicity

Provided is an adeno-associated virus (AAV) complex for expression of an RUNX3 gene including an asymmetrically modified inverted terminal repeat (ITR). The AAV complex has asymmetric ITRs in which one of the two ITRs is modified, thereby increasing self-replication efficiency in host cells and increasing expression efficiency of a delivered gene, and therefore, compared to existing AAV complexes, the AAV complex has an advantage of improved productivity and gene expression efficiency.

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Cheongju-si, South Korea

Suk Chul Bae