Asahi Kasei Kabushiki Kaisha

Amsterdam Molecular Therapeutics B.v.

Genesis Healthcare Corp.

Uniqure IP B.v.

Keiya Ozawa

Akira Itoh

Yutaka Hanazono

Takashi Okada

Wilhelmus Theodorus Johannes Maria Christiaan Hermens

Saskia Jacoba Petronella Haast

Masashi Urabe

Wilhelmus Theodorus Johannes Maria Christian Hermens

Wilhelmus TJMC Hermens

The present invention relates to the production of adeno-associated viral vectors in insect cells. The insect cells therefore comprise a first nucleotide sequence encoding the adeno-associated virus (AAV) capsid proteins, whereby the initiation codon for translation of the AAV VP1 capsid protein is a non-ATG, suboptimal initiation codon. The insect cell further comprises a second nucleotide sequence comprising at least one AAV inverted terminal repeat (ITR) nucleotide sequence; a third nucleotide sequence comprising a Rep52 or a Rep40 coding sequence operably linked to expression control sequences for expression in an insect cell; and, a fourth nucleotide sequence comprising a Rep78 or a Rep68 coding sequence operably linked to expression control sequences for expression in an insect cell. The invention further relates to adeno-associated viral vectors with an altered ratio of the viral capsid proteins that provides improved infectivity of the viral particles.

AAV vectors produced in insect cells

A gene transfer efficiency enhancer of the present invention which contains a histone deacetylase inhibitor (especially compound (A)) as an active ingredient is capable of enhancing gene transfer efficiency in a gene transfer mediated by an adeno-associated virus vector while retaining the advantages of the adeno-associated virus vector.

Gene introduction efficiency enhancer

The object of the present invention is to provide an agent for specific adsorption of type 5 adenoviral vector to undifferentiated blood cells which enables infection with a viral concentration that does not impart toxicity to undifferentiated blood cells, without requiring the construction of a new viral genome, or special modification of viral particles such as biotination, etc. The above objective has been achieved by providing a polypeptide which has affinity for both adenovirus and undifferentiated blood cells. Use of the polypeptide of the present invention enables improved efficiency of adenoviral vector-mediated gene transfer of any gene to undifferentiated blood cells, and there is provided a method of introducing any gene for which transient expression in these cells is desired. In particular, the method is useful for intracellular DNA recombination by transiently expressing site-specific recombinase, and for induction into any cells of different lines by transient expression of master genes.

Agents for adsorption and bridging for adenovirus

Disclosed is an expression control system with which any gene of interest can be transferred into mammalian cells to thereby change the nature thereof and the gene can be excised at any time by administering a low molecular weight compound to the cells. Specifically disclosed is a vector satisfying specific requirements when inserted into the genome of a mammalian cell.

Vector for reversible gene integration

Growing community of inventors

Tochigi, Japan

Keiya Ozawa