	US 11,859,190 B2
	Methods and compositions for regulation of transgene expression
Edward J. Rebar, Brisbane, CA (US)
Assigned to Sangamo Therapeutics, Inc., Brisbane, CA (US)
Filed by Sangamo Therapeutics, Inc., Brisbane, CA (US)
Filed on Mar. 3, 2021, as Appl. No. 17/190,994.
Application 14/832,434 is a division of application No. 13/624,217, filed on Sep. 21, 2012, granted, now 9,150,847, issued on Oct. 6, 2015.
Application 17/190,994 is a continuation of application No. 15/690,067, filed on Aug. 29, 2017, granted, now 10,975,375.
Application 15/690,067 is a continuation of application No. 14/832,434, filed on Aug. 21, 2015, granted, now 9,777,281, issued on Oct. 3, 2017.
Claims priority of provisional application 61/670,490, filed on Jul. 11, 2012.
Claims priority of provisional application 61/560,506, filed on Nov. 16, 2011.
Claims priority of provisional application 61/537,349, filed on Sep. 21, 2011.
Prior Publication US 2021/0189405 A1, Jun. 24, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. C12N 15/62 (2006.01); C07K 14/00 (2006.01); C12N 9/22 (2006.01); C12N 9/96 (2006.01); C12N 15/85 (2006.01)

CPC C12N 15/62 (2013.01) [C07K 14/00 (2013.01); C12N 9/22 (2013.01); C12N 9/96 (2013.01); C12N 15/85 (2013.01); C07K 2319/81 (2013.01); C12N 2799/025 (2013.01)]

5 Claims

1. A polynucleotide comprising a sequence encoding a non-naturally occurring fusion protein comprising a zinc finger DNA-binding protein that binds to an endogenous albumin gene and a cleavage domain, wherein the non-naturally occurring fusion protein cleaves the endogenous albumin gene and further wherein the zinc finger DNA-binding protein comprises 4, 5 or 6 zinc finger domains, each zinc finger domain comprising a recognition helix region, wherein the zinc finger domains comprise the recognition helix regions in the order shown in a single row of the following Table:


F1	F2	F3

TSGSLTR	RSDALST	QSATRTK
(SEQ ID	(SEQ ID	(SEQ ID
NO: 1)	NO: 2)	NO: 3)

RSDHLSA	TKSNRTK	DRSNLSR
(SEQ ID	(SEQ ID	(SEQ ID
NO: 6)	NO: 7)	NO: 8)

TSGNLTR	DRSTRRQ	TSGSLTR
(SEQ ID	(SEQ ID	(SEQ ID
NO: 11)	NO: 12)	NO: 1)

DRSALAR	RSDHLSE	HRSDRTR
(SEQ ID	(SEQ ID	(SEQ ID
NO: 15)	NO: 16)	NO: 17)

RSDNLST	DRSALAR	DRSNLSR
(SEQ ID	(SEQ ID	(SEQ ID
NO: 20)	NO: 15)	NO: 8)

DRSNLSR	LKQVLVR	QSGNLAR
(SEQ ID	(SEQ ID	(SEQ ID
NO: 8)	NO: 24)	NO: 5)

DRSNLSR	DGRNLRH	RSDNLAR
(SEQ ID	(SEQ ID	(SEQ ID
NO: 8)	NO: 21)	NO: 22)

RSDNLSV	HSNARKT	RSDSLSA
(SEQ ID	(SEQ ID	(SEQ ID
NO: 26)	NO: 27)	NO: 28)

RSDNLSE	ERANRNS	QSANRTK
(SEQ ID	(SEQ ID	(SEQ ID
NO: 30)	NO: 31)	NO: 32)

TSGSLTR	DRSNLSR	DGRNLRH
(SEQ ID	(SEQ ID	(SEQ ID
NO: 1)	NO: 8)	NO: 21)

QSGHLAR	RSDHLTQ	RSDHLSQ
(SEQ ID	(SEQ ID	(SEQ ID
NO: 34)	NO: 35)	NO: 36)

QSGDLTR	RSDALAR	QSGDLTR
(SEQ ID	(SEQ ID	(SEQ ID
NO: 40)	NO: 41)	NO: 40)

RSDNLSV	YSSTRNS	RSDHLSA
(SEQ ID	(SEQ ID	(SEQ ID
NO: 26)	NO: 44)	NO: 6)

RSDNLST	QKSPLNT	TSGNLTR
(SEQ ID	(SEQ ID	(SEQ ID
NO: 20)	NO: 48)	NO: 11)

RSDNLSV	RRAHLNQ	TSGNLTR
(SEQ ID	(SEQ ID	(SEQ ID
NO: 26)	NO: 50)	NO: 11)

DSSDRKK	DRSALSR	TSSNRKT
(SEQ ID	(SEQ ID	(SEQ ID
NO: 10)	NO: 52)	NO: 53)

QSSDLSR	LRHNLRA	DQSNLRA
(SEQ ID	(SEQ ID	(SEQ ID
NO: 46)	NO: 105)	NO: 106)

QSSDLSR	HRSNLNK	DQSNLRA
(SEQ ID	(SEQ ID	(SEQ ID
NO: 46)	NO: 108)	NO: 106)

QSSDLSR	LKWNLRT	DQSNLRA
(SEQ ID	(SEQ ID	(SEQ ID
NO: 46)	NO: 109)	NO: 106)

QSSDLSR	LRHNLRA	DQSNLRA
(SEQ ID	(SEQ ID	(SEQ ID
NO: 46)	NO: 105)	NO: 106)

QSSDLSR	HRSNLNK	DQSNLRA
(SEQ ID	(SEQ ID	(SEQ ID
NO: 46)	NO: 108)	NO: 106)

QSSDLSR	WKWNLRA	DQSNLRA
(SEQ ID	(SEQ ID	(SEQ ID
NO: 46)	NO: 110)	NO: 106)

QSGNLAR	LMQNRNQ	LKQHLNE
(SEQ ID	(SEQ ID	(SEQ ID
NO: 5)	NO: 97)	NO: 111)

QSGNLAR	HLGNLKT	LKQHLNE
(SEQ ID	(SEQ ID	(SEQ ID
NO: 5)	NO: 94)	NO: 111)

QSGNLAR	LMQNRNQ	LKQHLNE
(SEQ ID	(SEQ ID	(SEQ ID
NO: 5)	NO: 97)	NO: 111)

QRSNLVR	TSSNRKT	LKHHLTD
(SEQ ID	(SEQ ID	(SEQ ID
NO: 99)	NO: 53)	NO: 95)

DKSYLRP	TSGNLTR	HRSARKR
(SEQ ID	(SEQ ID	(SEQ ID
NO: 114)	NO: 11)	NO: 115)

TSGNLTR	HRSARKR	QSGDLTR
(SEQ ID	(SEQ ID	(SEQ ID
NO: 11)	NO: 115)	NO: 40)

QSGDLTR	QSGNLHV	QSAHRKN
(SEQ ID	(SEQ ID	(SEQ ID
NO: 40)	NO: 117)	NO: 118)

QSGDLTR	QRSNLNI	QSAHRKN
(SEQ ID	(SEQ ID	(SEQ ID
NO: 40)	NO: 121)	NO: 118)

QRSNLDS	QSSDLSR	YHWYLKK
(SEQ ID	(SEQ ID	(SEQ ID
NO: 83)	NO: 46)	NO: 84)

QSGNLAR	QYTHLVA	RSDHLST
(SEQ ID	(SEQ ID	(SEQ ID
NO: 5)	NO: 87)	NO: 88)

QSGNLAR	HLGNLKT	LKHHLTD
(SEQ ID	(SEQ ID	(SEQ ID
NO: 5)	NO: 94)	NO: 95)

QSGNLAR	LMQNRNQ	LKHHLTD
(SEQ ID	(SEQ ID	(SEQ ID
NO: 5)	NO: 97)	NO: 95)

QRSNLVR	LRMNLTK	LKHHLTD
(SEQ ID	(SEQ ID	(SEQ ID
NO: 99)	NO: 100)	NO: 95)

QRSNLVR	LRMNLTK	LKHHLTD
(SEQ ID	(SEQ ID	(SEQ ID
NO: 99)	NO: 100)	NO: 95)

QSGNLAR	LMQNRNQ	LKHHLTD
(SEQ ID	(SEQ ID	(SEQ ID
NO: 5)	NO: 97)	NO: 95)

F4	F5	F6

TSGHLSR	QSGNLAR	NA
(SEQ ID	(SEQ ID
NO: 4)	NO: 5)

WRSSLRA	DSSDRKK	NA
(SEQ ID	(SEQ ID
NO: 9)	NO: 10)

ERGTLAR	TSANLSR	NA
(SEQ ID	(SEQ ID
NO: 13)	NO: 14)

QSGALAR	QSGHLSR	NS
(SEQ ID	(SEQ ID
NO: 18)	NO: 19)

DGRNLRH	RSDNLAR	QSNALNR
(SEQ ID	(SEQ ID	(SEQ ID
NO: 21)	NO: 22)	NO: 23)

QSTPLFA	QSGALAR	NA
(SEQ ID	(SEQ ID
NO: 25)	NO: 18)

QSNALNR	NA	NA
(SEQ ID
NO: 23)

QSGNLAR	RSDSLSV	QSGHLSR
(SEQ ID	(SEQ ID	(SEQ ID
NO: 5)	NO: 29)	NO: 19)

ERGTLAR	RSDALTQ	NA
(SEQ ID	(SEQ ID
NO: 13)	NO: 33)

ERGTLAR	RSDAITQ	NA
(SEQ ID	(SEQ ID
NO: 13)	NO: 33)

WRSSLVA	RSDVLSE	RNQHRKT
(SEQ ID	(SEQ ID	(SEQ ID
NO: 37)	NO: 38)	NO: 39)

RRDPLIN	RSDNLSV	IRSTLRD
(SEQ ID	(SEQ ID	(SEQ ID
NO: 42)	NO: 26)	NO: 43)

SYWSRTV	QSSDLSR	RTDALRG
(SEQ ID	(SEQ ID	(SEQ ID
NO: 45)	NO: 46)	NO: 47)

QAENLKS	QSSDLSR	RTDALRG
(SEQ ID	(SEQ ID	(SEQ ID
NO: 49)	NO: 46)	NO: 47)

SDTNRFK	RSDNLST	QSGHLSR
(SEQ ID	(SEQ ID	(SEQ ID
NO: 51)	NO: 20)	NO: 19)

QSGALAR	RSDHLSR	NA
(SEQ ID	(SEQ ID
NO: 18)	NO: 54)

RPYTLRL	QSSDLSR	HRSNLNK
(SEQ ID	(SEQ ID	(SEQ ID
NO: 107)	NO: 46)	NO: 108)

RPYTLRL	QSSDLSR	HRSNLNK
(SEQ ID	(SEQ ID	(SEQ ID
NO: 107)	NO: 46)	NO: 108)

RPYTLRL	QSSDLSR	HRSNLNK
(SEQ ID	(SEQ ID	(SEQ ID
NO: 107)	NO: 46)	NO: 108)

RPYTLRL	QSSDLSR	HRSNLNK
(SEQ ID	(SEQ ID	(SEQ ID
NO: 107)	NO: 46)	NO: 108)

RPYTLRL	QSSDLSR	HRSNLNK
(SEQ ID	(SEQ ID	(SEQ ID
NO: 107)	NO: 46)	NO: 108)

RPYTLRL	QSSDLSR	HRSNLNK
(SEQ ID	(SEQ ID	(SEQ ID
NO: 107)	NO: 46)	NO: 108)

TSGNLTR	RRYYLRL	N/A
(SEQ ID	(SEQ ID
NO: 11)	NO: 112)

TSGNLTR	RRDWRRD	N/A
(SEQ ID	(SEQ ID
NO: 11)	NO: 113)

TSGNLTR	RRDWRRD	N/A
(SEQ ID	(SEQ ID
NO: 11)	NO: 113)

TSGNLTR	RRDWRRD	N/A
(SEQ ID	(SEQ ID
NO: 11)	NO: 113)

QSSDLSR	WRSSLKT	N/A
(SEQ ID	(SEQ ID
NO: 46)	NO: 116)

NRHHLKS	N/A	N/A
(SEQ ID
NO: 163)

STAALSY	TSGSLSR	RSDALAR
(SEQ ID	(SEQ ID	(SEQ ID
NO: 119)	NO: 120)	NO: 41)

STAALSY	DRSALSR	RSDALAR
(SEQ ID	(SEQ ID	(SEQ ID
NO: 119)	NO: 52)	NO: 41)

RSDDLSV	TSSNRTK	N/A
(SEQ ID	(SEQ ID
NO: 85)	NO: 86)

RSDARTT	DRSALAR	N/A
(SEQ ID	(SEQ ID
NO: 89)	NO: 15)

DRSNLSR	RLDNRTA	N/A
(SEQ ID	(SEQ ID
NO: 8)	NO: 96)

DRSNLSR	RSDHLTT	N/A
(SEQ ID	(SEQ ID
NO: 8)	NO: 98)

DRSNLSR	RSDHLTT	N/A
(SEQ ID	(SEQ ID
NO: 8)	NO: 98)

DRSNLSR	RSDHLTQ	N/A
(SEQ ID	(SEQ ID
NO: 8)	NO: 35)

DRSNLSR	RSDHLTQ	N/A.
(SEQ ID	(SEQ ID
NO: 8)	NO: 35)