Tel Aviv University

Ramot University Authority for Applied Research and Industrial Development Limited

Iris Dotan

Dan Canaani

Arnold Simons

Naomi Dafni

Adi Barzel

Miriam Fried

Daniel Nataf

Ronni Aram

Carmel Pundak-Mintz

Natalia Gritsenko

Pnina Gottfried Komlosh

Yoram Oron

The present invention relates to methods for targeted insertion of at least one nucleic acid sequence/s of interest into a target genomic locus of a mammalian cell. More specifically, the methods of the invention are based on using nucleic acid cassettes comprising the nucleic acid sequence/s of interest and at least one recognition signal sequence (RSS), for insertion of the nucleic acid sequence of interest into the target genomic locus that is mediated by RAG-catalyzed recombination. The invention further provides cassettes, vectors and vehicles and cells comprising said cassettes, compositions and uses thereof in immunotherapy.

Recombination activating gene (RAG) induced V(D)J gene targeting

The invention provides modulators of human cancer and tumor metastasis in particular. More specifically the present disclosure relates to modulators of SKAI1BC, an antisense long non-coding RNA which was found to be an epigenetic suppressor of the metastasis suppressor gene KAI1/CD82, compositions, methods and uses thereof for decreasing metastasis, invasion and possibly also proliferation of cancer cells.

Modulators of human KAI1 metastasis suppressor gene, methods and uses thereof

A method for screening molecule which have a synthetic lethal property when in combination with a gene of interest carrying a non-lethal mutation, said method comprising the steps of: transfecting a first reporter gene into mammalian cells having a genome comprising a gene of interest which carries a non-lethal mutation, or a genome which is null of said gene of interest; selecting clones stably expressing said fist reporter gene; introducing into said cells a survival plasmid comprising a functioning copy of said gene of interest, a second reporter gene, selectable marker, an origin of DNA replication and a nuclear antigen gene essential for replication of the plasmid within said cells, wherein said survivsal plasmid is autonomously replicating and spontaneously lost from said cells; growing said cells in the presence of a selection compound which selects for said selectable marker; selecting cell clones stably expressing said second reporter gene and said functioning copy of said gene of interest; removing selection for the selectable marker, and adding molecules destined for screening of their ability to impose selective pressure enforcing retention of the unstable survival plasmid, determining survival plasmid retention in cells, thus identifying a molecule having a synthetic lethal property when in combination with non lethal mutated gene of interest.

Genetic screening methods

A screening method which applies the principle of synthetic lethality to a gene of interest in non-yeast eukaryotic cells. The method may be used to screen either a chemical library in order to identify a molecule having a gene-specific lethal property in the cells, or to screen a group of DNA molecules in order to identify among them one or more modulators of gene function which are synergistically lethal to the cells together with an incapacitated gene of interest. Also described are episomal survival plasmids and kits which may be used with the method.

Growing community of inventors

Tel Aviv, Israel

Iris Dotan