The present invention relates to a tomato plant which carries at least one QTL in its genome that leads to its fruits comprising higher levels of anthocyanins when compared to fruits produced by a tomato plant not carrying said QTL in its genome, wherein said fruits are not purple at the red-ripe harvest stage. A tomato plant of the invention may also comprise all QTLs, each either in homozygous or heterozygous form. The invention further relates to progeny of the plant, propagation material for the plant and to markers for identifying the QTLs and their use.

A method of eliminating the risk of JCV activation in a subject undergoing immunosuppressive therapy, by administering an effective amount of a gene editing composition directed toward at least one target sequence in the JCV genome, cleaving the target sequence in the JCV genome, disrupting the JCV genome, eliminating the JCV infection, eliminating the risk of JCV activation, and treating the subject with an immunosuppressive therapy. A pharmaceutical composition including at least one isolated nucleic acid sequence encoding a CRISPR-associated endonuclease and at least one gRNA having a spacer sequence complementary to a target sequence in a JCV DNA, the isolated nucleic acid sequences being included in at least one expression vector. Pharmaceutical compositions including at least one isolated nucleic acid sequence encoding at least one TALEN, at least one ZFN, and gene editing composition of C2c1, C2c3, TevCas9, Archaea Cas9, CasY.1-CasY.6, CasX, or argonaute protein, which target at least one nucleotide sequence of the JCV genome.

A method of eliminating the risk of JCV activation in a subject undergoing immunosuppressive therapy, by administering an effective amount of a gene editing composition directed toward at least one target sequence in the JCV genome, cleaving the target sequence in the JCV genome, disrupting the JCV genome, eliminating the JCV infection, eliminating the risk of JCV activation, and treating the subject with an immunosuppressive therapy. A pharmaceutical composition including at least one isolated nucleic acid sequence encoding a CRISPR-associated endonuclease and at least one gRNA having a spacer sequence complementary to a target sequence in a JCV DNA, the isolated nucleic acid sequences being included in at least one expression vector. Pharmaceutical compositions including at least one isolated nucleic acid sequence encoding at least one TALEN, at least one ZFN, and gene editing composition of C2c1, C2c3, TevCas9, Archaea Cas9, CasY.1-CasY.6, CasX, or argonaute protein, which target at least one nucleotide sequence of the JCV genome.

The invention relates to methods of modifying DNA methylation by contacting a cell with a catalytically inactive site specific nuclease fused to an effector domain having methylation or demethylation activity and one or more guide sequences.

A method for maintaining a male sterile plant in a homozygous recessive state includes providing a first plant that includes homozygous recessive male sterility alleles, providing a second plant that includes homozygous recessive male sterility alleles the same as that in the first plant and a nucleotide construct in which the construct exists in a heterozygous state. The first nucleotide sequence of the nucleotide construct encodes a first protein that restores male fertility of the first plant after expression in the first plant. The second nucleotide sequence of the nucleotide construct allows for distinguishing the grains with or without the construct by observation through naked eyes or devices. The first nucleotide sequence and the second nucleotide sequence are tightly connected with each other and coexist in a plant. The method further includes fertilizing female gametes of the first plant with male gametes of the second plant.

A method for maintaining a male sterile plant in a homozygous recessive state includes providing a first plant that includes homozygous recessive male sterility alleles, providing a second plant that includes homozygous recessive male sterility alleles the same as that in the first plant and a nucleotide construct in which the construct exists in a heterozygous state. The first nucleotide sequence of the nucleotide construct encodes a first protein that restores male fertility of the first plant after expression in the first plant. The second nucleotide sequence of the nucleotide construct allows for distinguishing the grains with or without the construct by observation through naked eyes or devices. The first nucleotide sequence and the second nucleotide sequence are tightly connected with each other and coexist in a plant. The method further includes fertilizing female gametes of the first plant with male gametes of the second plant.

Genetically engineered hematopoietic cells such as hematopoietic stem cells having one or more genetically edited genes of lineage-specific cell-surface proteins and therapeutic uses thereof, either alone or in combination with immune therapy that targets the lineage-specific cell-surface proteins.

The present invention encompasses engineered nucleases which recognize and cleave a recognition sequence within a Hepatitis B virus (HBV) genome. The engineered meganucleases can exhibit at least one optimized characteristic, such as enhanced specificity and/or efficiency of indel formation, when compared to previously described HBV meganucleases. Further, the invention encompasses pharmaceutical compositions comprising engineered meganuclease proteins, nucleic acids encoding engineered meganucleases, and the use of such compositions for treating HBV infections or hepatocellular carcinoma.

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 antibody sequences found in antibodies that bind to human CD38. In particular, the present disclosure provides sequences of anti-human CD38 antibodies. Antibodies and antigen-binding portions thereof including such sequences present features compatible with pharmaceutical manufacturing and development can be provided as fully human antibodies (e.g., fully human monoclonal antibodies or antigen-binding fragments) that can be useful for medical methods and compositions, in particular for treating cancer.