Provided are transgenic Caenorhabditis elegans (C. elegans) overexpressing DNA methyltransferase 3a (Dnmt3a) and a method of producing the same. According to the method, a specific mechanism and related factors for DNA methylation mediated by Dnmt3a may be found, and a critical gene for regulating the life span of C. elegans may be identified, and therefore C. elegans may be used as an animal model for screening a drug for a DNA methylation-related disease.

Provided are transgenic Caenorhabditis elegans (C. elegans) overexpressing DNA methyltransferase 3a (Dnmt3a) and a method of producing the same. According to the method, a specific mechanism and related factors for DNA methylation mediated by Dnmt3a may be found, and a critical gene for regulating the life span of C. elegans may be identified, and therefore C. elegans may be used as an animal model for screening a drug for a DNA methylation-related disease.

Described are Caenorhabditis elegans (C. elegans) strains exhibiting an RNA toxicity phenotype. The C. elegans strains comprise a detectable reporter gene expressed in one or more cell types, with the expressed reporter gene RNA having in instance of at least fifty oligonucleotide repeats (e.g., trinucleotide repeats). Exemplary C. elegans reporter strains are generated that exhibit phenotypes characteristic of the human disorder Myotonic Dystrophy 1. The C. elegans strains are amenable for high-throughput screening applications, for both gene target as well as small molecule identification.

Entomopathogenic nematode Heterorhabditis bacteriophora having an enhanced longevity, comprising a first locus comprising a single nucleotide polymorphism at position 75 of the nucleotide sequence SC00004647 as depicted in SEQ ID NO: 5, in which C is substituted by T; and/or a second locus comprising a single nucleotide polymorphism at position 54 of the nucleotide sequence SC00006203 as depicted in SEQ ID NO: 7, in which C is substituted by T.

Entomopathogenic nematode Heterorhabditis bacteriophora having an enhanced longevity, comprising a first locus comprising a single nucleotide polymorphism at position 75 of the nucleotide sequence SC00004647 as depicted in SEQ ID NO: 5, in which C is substituted by T; and/or a second locus comprising a single nucleotide polymorphism at position 54 of the nucleotide sequence SC00006203 as depicted in SEQ ID NO: 7, in which C is substituted by T.

Provided herein are genetically modified cells and methods of their production, wherein such methods include introducing a nucleic acid molecule including a plurality of index sequences into a cell comprising a synthetic landing pad, wherein each of the plurality of index sequences includes a first portion of a sequence and the synthetic landing pad includes a second portion of the sequence. The method further includes generating a plurality of cells that include the synthetic landing pad and the nucleic acid molecule including the plurality of index sequences and integrating one of the plurality of index sequences into the synthetic landing pad in each of the cells, thereby linking the first and second portions of the sequence. The linked first and second portions of the sequence result in a functional gene and cells including the integrated index sequence are selected based on presence or activity of the functional gene.

Provided herein are genetically modified cells and methods of their production, wherein such methods include introducing a nucleic acid molecule including a plurality of index sequences into a cell comprising a synthetic landing pad, wherein each of the plurality of index sequences includes a first portion of a sequence and the synthetic landing pad includes a second portion of the sequence. The method further includes generating a plurality of cells that include the synthetic landing pad and the nucleic acid molecule including the plurality of index sequences and integrating one of the plurality of index sequences into the synthetic landing pad in each of the cells, thereby linking the first and second portions of the sequence. The linked first and second portions of the sequence result in a functional gene and cells including the integrated index sequence are selected based on presence or activity of the functional gene.

The present disclosure provides transgenic nematode systems for assessing function of heterologous genes, their variants and drug discovery. The transgenic nematodes contain a heterologous gene that is inserted via homologous recombination at the native locus replacing and removing the nematode ortholog, wherein expression of the heterologous gene rescues function of the removed nematode ortholog and a transgenic control animal is provided. The heterologous gene may be further modified to provide a variant, such as a human clinical variant, whereby a transgenic test animal is provided. Those transgenic test animals are used in methods to assess function of the heterologous variant and drug screens to find therapeutic candidates reversing deviant activity back to wildtype.

The present disclosure provides transgenic nematode systems for assessing function of heterologous genes, their variants and drug discovery. The transgenic nematodes contain a heterologous gene that is inserted via homologous recombination at the native locus replacing and removing the nematode ortholog, wherein expression of the heterologous gene rescues function of the removed nematode ortholog and a transgenic control animal is provided. The heterologous gene may be further modified to provide a variant, such as a human clinical variant, whereby a transgenic test animal is provided. Those transgenic test animals are used in methods to assess function of the heterologous variant and drug screens to find therapeutic candidates reversing deviant activity back to wildtype.

The present disclosure provides transgenic nematode systems for assessing function of heterologous genes, their variants and drug discovery. The transgenic nematodes contain a heterologous gene that is inserted via homologous recombination at the native locus replacing and removing the nematode ortholog, wherein expression of the heterologous gene rescues function of the removed nematode ortholog and a transgenic control animal is provided. The heterologous gene may be further modified to provide a variant, such as a human clinical variant, whereby a transgenic test animal is provided. Those transgenic test animals are used in methods to assess function of the heterologous variant and drug screens to find therapeutic candidates reversing deviant activity back to wildtype.