DNA sequence modification-based gene drive

A vector, comprising:

• a first gene sequence encoding a DNA sequence modifying enzyme, wherein the DNA sequence modifying enzyme induces one or more sequence modifications in an endogenous copy of an essential gene, wherein the DNA sequence modifying enzyme is Cas9 nuclease;
• a first promoter operably linked to the first gene sequence encoding the DNA sequence modifying enzyme, wherein the first promoter is selected from the group consisting of a germline promoter, a male specific germline promoter, and a female specific germline promoter;
• a second rescue transgene sequence;
• a second promoter operably linked to the rescue transgene sequence;
• a sequence encoding at least one guide RNA, wherein the guide RNA enables the Cas9 nuclease to target specific sequences within the essential gene,
• one or more additional sequences that allow the vector to be positioned in a chromosome or an extra-chromosomal element that is different from the location of the endogenous copy of the essential gene comprise sequences that are not homologous to sequences flanking the endogenous copy of the essential gene, and
• one or more cargo sequences;
• wherein the one or more sequence modifications being cleavage of the essential gene resulting in the essential gene being rendered partially or wholly non-functional and resulting in a defect in survival, growth control, fertility, or differentiation in absence of the rescue transgene,
• wherein a rescue of the defect occurs by the rescue transgene being positioned in a chromosomal or an extrachromosomal element that is different from the location of the endogenous copy of the essential gene,
• wherein the rescue transgene is either a recoded copy of the essential gene or is a gene of unrelated sequence,
• wherein the rescue transgene encodes a protein that is functionally equivalent to a protein encoded by the essential gene, and wherein the DNA sequence modifying enzyme does not modify the rescue transgene, and
• wherein the vector is capable of performing a gene spread by increasing in relative frequency in a population following introduction into an organism by causing the death of those who inherit only non-functional alleles of the essential gene and fail to inherit the vector.