The invention relates to a recombinant baculoviral genome useful for the production of viral vectors for gene therapy, allowing said production from a single infection

Described herein are engineered nodaviral vectors, systems, and uses thereof. In some embodiments, the engineered nodaviral vectors and/or systems can be used to deliver a cargo, such as a nucleic acid cargo, to a cell or cell population, or a subject. In some embodiments, the cargo is a therapeutic or preventative.

Provided herein is a baculovirus expression vector system for the production of a desired protein. In one aspect, the desired protein is a closed-ended DNA (ceDNA) molecule comprising wild-type and/or truncated inverted terminal repeats derived from a genome of a member of the viral family Parvoviridae.

The present invention relates nucleic acid constructs for the production of recombinant parvoviral (e.g. adeno-associated viral) vectors in insect cells, to insect cells comprising such constructs and to methods wherein the cells are used to produce recombinant parvoviral virions. The insect cells preferably comprise a first nucleotide sequence encoding the parvoviral rep proteins whereby the initiation codon for translation of the parvoviral Rep78 protein is a suboptimal initiation codon that effects partial exon skipping upon expression in insect cells. The insect cell further comprises a second nucleotide sequence comprising at least one parvoviral (AA V) inverted terminal repeat (ITR) nucleotide sequence and a third nucleotide sequence comprising a sequences coding for the parvoviral capsid proteins.

The present disclosure provides a novel genetically modified high productivity VVK-V432C insect cell line derived from the ATCC CRL-1711 cell line. Methods for obtaining this high productivity cell line are also provided.

The invention relates to a recombinant baculoviral genome useful for the production of viral vectors for gene therapy, allowing said production from a single infection.

A recombinant baculovirus, including: an adeno-associated virus Rep gene, an adeno-associated virus Cap gene, and an recombinant adeno-associated virus genome ITR-GOI (gene of interest) flanked by rAAV inverted terminal repeats (ITR). The ITR-GOI includes a 5 terminal nucleic acid fragment and a 3 terminal nucleic acid fragment. The ITR-GOI is linked to an expression cassette of the Cap gene and an expression cassette of the Rep gene through the 5 terminal nucleic acid fragment and the 3 terminal nucleic acid fragment, respectively.

A method for producing a recombinant adeno-associated virus (rAAV) and a recombinant baculovirus virus, the method including: (1) infecting an insect host packaging cell line with a corresponding recombinant baculovirus integrated with an rAAV genome ITR-GOI (gene of interest flanked by AAV inverted terminal repeats) and an AAV Cap gene or AAV Rep gene; (2) culturing the host packaging cell line infected with the recombinant baculovirus, so as to produce the recombinant adeno-associated virus; and (3) separating and purifying the recombinant adeno-associated virus obtained in (2).

The present invention relates nucleic acid constructs for the production of recombinant parvoviral (e.g. adeno-associated viral) vectors in insect cells, to insect cells comprising such constructs and to methods wherein the cells are used to produce recombinant parvoviral virions. The insect cells preferably comprise a first nucleotide sequence encoding the parvoviral rep proteins whereby the initiation codon for translation of the parvoviral Rep78 protein is a suboptimal initiation codon that effects partial exon skipping upon expression in insect cells. The insect cell further comprises a second nucleotide sequence comprising at least one parvoviral (AA V) inverted terminal repeat (ITR) nucleotide sequence and a third nucleotide sequence comprising a sequences coding for the parvoviral capsid proteins.

The present invention provides a recombinant foot and mouth disease virus (FMDV) capsid precursor protein comprising a modified VP1 protein and optionally further comprising a modified VP4 protein. The invention further relates to an isolated nucleic acid molecule and an expression vector comprising the nucleic acid molecule for recombinant expression of the modified capsid precursor protein. In further aspects, the invention relates to a virus-like particle (VLP) obtained from the modified capsid precursor protein and a vaccine for use in the protection of a subject against an infection with FMDV produced from the VLP.