Abstract: An active genetic approach to preferentially transmit allelic variants (allelic-drive) resulting from only a single or a few nucleotide alterations. Embodiments are provided for allelic-drive: one, copy-cutting, in which a non-preferred allele is selectively targeted for Cas9/guide RNA (gRNA) cleavage, and a more general approach, copy-grafting, that permits selective inheritance of a desired allele located at some distance from the gRNA cut site. A lethal mosaicism is provided that dominantly eliminates NHEJ-induced mutations and favors inheritance of functional cleavage-resistant alleles. These two efficient allelic-drive methods, enhanced by lethal mosaicism and a trans-generational drive process provide a shadow-drive, that are applicable to improvements in health and agriculture.

Abstract: Described herein are methods and compositions for autocatalytic genome editing and neutralizing autocatalytic genome editing. The autocatalytic genome editing may be based on genomic integration of a construct containing multiple elements or on a trans-complementation approach, in which genetic elements can be propagated separately. The disclosure provides a method for autocatalytic genome editing based on the CRISPR/CAS9 system, and methods of use thereof, in animals, humans, and plants for eliminating pathogens, targeting suppression of crop pests, strategies to combat virus (e.g., HIV) and other diseases (e.g., cancer) caused by retrovirus, as well as to generate homozygous mutations that are transmitted to nearly all offspring.

Abstract: Provided are systems, constructs, genetically modified organisms, and methods for greatly reducing or eliminating local populations of Aedes aegypti mosquitoes, and associated Dengue fever, yellow fever, Zika virus, and Chikungunya virus. Provided are genetically modified Aedes aegypti having a Cas9-mediated split gene-drive system for masculinizing the mosquito and ensuring that any female carries a sterile mutation. In addition, gRNAs direct Cas9 cleavage of insecticide-resistance loci, rendering female mosquitoes escaping the male converting gene drive sensitive to insecticides.

Abstract: Provided are systems, constructs, genetically modified organisms, and methods for creating transgenic rodent research and commercial models of human physiology, disease, syndromes, and disorders. Provided are genetically modified rodents encoding for an sgRNA useful in a Cas9-mediated split gene-drive system for optimization of the gene drive system in rodents.

Abstract: Described herein are methods and compositions for autocatalytic genome editing and neutralizing autocatalytic genome editing. The autocatalytic genome editing may be based on genomic integration of a construct containing multiple elements or on a trans-complementation approach, in which genetic elements can be propagated separately. The disclosure provides a method for autocatalytic genome editing based on the CRISPR/CAS9 system, and methods of use thereof, in animals, humans, and plants for eliminating pathogens, targeting suppression of crop pests, strategies to combat virus (e.g., HIV) and other diseases (e.g., cancer) caused by retrovirus, as well as to generate homozygous mutations that are transmitted to nearly all offspring.

Abstract: The invention provides methods for autocatalytic genome editing based on genomic integration of a construct containing multiple elements. More specifically, the invention provides a method for autocatalytic genome editing or for deleting or neutralizing autocatalytic genome editing based on the CRISPR/Cas9 system, and methods of use thereof, in animals, humans, and plants for eliminating pathogens, targeting suppression of crop pests, strategies to combat virus (e.g., HIV) and other diseases (e.g., cancer) caused by retrovirus, as well as to generate, and reverse, homozygous mutations that are transmitted to nearly all offspring.