Peter E Lengyel, 84257 Central Park, New York, NY 10024

2013030, Nov 14, 2013

Jul 12, 2013

13/940609

Andrew J. Murphy - Croton-on-Hudson NY, US
Peter Matthew Lengyel - Brooklyn NY, US
Peter H.A. Yang - Tarrytown NY, US

C12N 15/90

435462, 4353201

Nucleic acid constructs and methods for rendering modifications to a genome are provided, wherein the modifications comprise null alleles, conditional alleles and null alleles comprising COINs. Multifunctional alleles (MFA) are provided, as well as methods for making them, which afford the ability in a single targeting to introduce an allele that can be used to generate a null allele, a conditional allele, or an allele that is a null allele and that further includes a COIN. MFAs comprise pairs of cognate recombinase recognition sites, an actuating sequence and/or a drug selection cassette, and a nucleotide sequence of interest, and a COIN, wherein upon action of a recombinase a conditional allele with a COIN is formed. In a further embodiment, action of a second recombinase forms an allele that contains only a COIN in sense orientation. In a further embodiment, action by a third recombinase forms an allele that contains only the actuating sequence in sense orientation.

2011010, May 5, 2011

Oct 29, 2010

12/915447

Aris N. Economides - Tarrytown NY, US
Andrew J. Murphy - Croton-on-Hudson NY, US
Peter Matthew Lengyel - Brooklyn NY, US
Peter H.A. Yang - Tarrytown NY, US

Regeneron Pharmaceuticals, Inc. - Tarrytown NY

C12N 5/10
C12N 15/85

435325, 4353201

Nucleic acid constructs and methods for rendering modifications to a genome are provided, wherein the modifications comprise null alleles, conditional alleles and null alleles comprising COINs. Multifunctional alleles (MFA) are provided, as well as methods for making them, which afford the ability in a single targeting to introduce an allele that can be used to generate a null allele, a conditional allele, or an allele that is a null allele and that further includes a COIN. MFAs comprise pairs of cognate recombinase recognition sites, an actuating sequence and/or a drug selection cassette, and a nucleotide sequence of interest, and a COIN, wherein upon action of a recombinase a conditional allele with a COIN is formed. In a further embodiment, action of a second recombinase forms an allele that contains only a COIN in sense orientation. In a further embodiment, action by a third recombinase forms an allele that contains only the actuating sequence in sense orientation.