Abstract

Genetic interactions (GIs) refer to the effect of one gene on a phenotype that is influenced by the presence/absence of one or more other genes. GIs can be either positive or negative and occur at various levels of genetic organization, such as within a gene, between genes within a pathway, or between different pathways.

There are multiple types of GIs. For example, synthetic interactions occur when the combination of two mutations leads to a phenotype that is more severe than either mutation alone. Synthetic lethality is an extreme example of a synthetic GI, in which the combination of mutations leads to cellular death. Or, epistatic interactions occur when one gene masks or modifies the effect of another gene on a phenotype. GIs can also be classified based on the level of genetic organization at which they occur (within a pathway, between pathways, or between chromosomes).

Combinatorial CRISPR screens are an essential method for finding genetic interactions at scale because they allow for the simultaneous targeting and manipulation of multiple genes in a cell or organism. Vivlion's proprietary 3Cs technology enables the generation of single and combinatorial CRISPR libraries for synthetic lethality and genetic interaction screening at scale, testing multi-million mutational combinations simultaneously. A unique ability that allows Vivlion to generate complex GI maps to i) assign genes to function, pathways, or complexes, ii) assign a function to uncharacterized genes, and iii) predict novel functions of known genes. Vivlion's ability to perform combinatorial CRISPR screens opens up new opportunities for drug discovery, as GIs can lead to novel drug targets and drug combinations.