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US 2024/0252598 A1Published application
Designed constitutively active cyclic gmp-amp synthase as a genetically encoded stimulant of interferons
AssigneeUniversity of Washington
InventorsQuinton M. DOWLING, Neil P. KING, Daniel Brewster STETSON, Hannah VOLKMAN, Elizabeth Erin GRAY
Life of this patent
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Abstract
The disclosure provides constitutively active Cyclic GMP-AMP Synthase (cGAS) polypeptide mutants and. methods for their use as adjuvants.
Claims22
A polypeptide comprising an amino acid sequence at least 20% identical to the amino acid sequence of SEQ ID NO:1 or 2,
- SEQ ID NO:
- 1
- (DAAP)GASKLRAVLEKLKLSRDDISTAAGMVKGVVDHLLLRLKCDSAFR
- GVGLLNTGSYYEHVKISAPNEFDVMFKLEVPRIQLEEYSNTRAYYFVKFK
- RNPKENPLSQFLEGEILSASKMLSKFRKIIKEEINDIKDTDVIMKRKRGG
- SPAVTLLISEKISVDITLALESKSSWPASTQEGLRIQNWLSAKVRKQLRL
- KPFYLVPKHAKEGNGFQEETWRLSFSHIEKEILNNHGKSKTCCENKEEKC
- CRKDCLKLMKYLLEQLKERFKDKKHLDKFSSYHVKTAFFHVCTQNPQDSQ
- WDRKDLGLCFDNCVTYFLQCLRTEKLENYFIPEFNLFSSNLIDKRSKEFL
- TKQIEYERNNEFPVFDEF
- (SEQ ID NO:
- 2)
- (M)QPWHGKAMQRASEAGATAPKASARNARGAPMDPTESPAAPEAALPKA
- GKFGPARKSGSRQKKSAPDTQERPPVRATGARAKKAPQRAQDTQPSDATS
- APGAEGLEPPAAREPALSRAGSCRQRGARCSTKPRPPPGPWDVPSPGLPV
- SAPILVRRDAAPGASKLRAVLEKLKLSRDDISTAAGMVKGVVDHLLLRLK
- CDSAFRGVGLLNTGSYYEHVKISAPNEFDVMFKLEVPRIQLEEYSNTRAY
- YFVKFKRNPKENPLSQFLEGEILSASKMLSKFRKIIKEEINDIKDTDVIM
- KRKRGGSPAVTLLISEKISVDITLALESKSSWPASTQEGLRIQNWLSAKV
- RKQLRLKPFYLVPKHAKEGNGFQEETWRLSFSHIEKEILNNHGKSKTCCE
- NKEEKCCRKDCLKLMKYLLEQLKERFKDKKHLDKFSSYHVKTAFFHVCTQ
- NPQDSQWDRKDLGLCFDNCVTYFLWCLRTEKLENYFIPEFNLFSSNLIDK
- RSKEFLTKQIEYERNNEFPVFDEF;
- wherein the polypeptide is a constitutively active Cyclic GMP-AMP Synthase (cGAS) mutant;
- wherein residues in parentheses are optional and may be present or absent;
- wherein relative to residue numbering in SEQ ID NO:1:
- residue 56 is G, residue 57 is S, residue 60 is E, residue 69 is E, and residue 71 is D;
- and
- wherein one or both of the following are true:
- (a) residue 19 is P and residue 20 is A;
- or residue 19 is D and residue 20 is P;
- and
- (b) residue 54 is P, L, or F and residue 58 is F, I, W, or L.
30 more elements
A polypeptide comprising an amino acid sequence at least 20% identical to the amino acid sequence of SEQ ID NO:3 or 4,
- (SEQ ID NO:
- 3)
- (SPD)KLKKVLDKLRLKRKDISEAAETVNKVVERLLRRMQKRESEEKGVE
- QLNTGSYYEHVKISAPNEFDVMFKLEVPRIELQEYYETGAFYLVKFKRIP
- RGNPLSHFLEGEVLSATKMLSKFRKIIKEEVKEIKDIDVSVEKEKPGSPA
- VTLLIRNPEEISVDIILALESKGSWPISTKEGLPIQGWLGTKVRTNLRRE
- PFYLVPKNAKDGNSFQGETWRLSFSHTEKYILNNHGIEKTCCESSGAKCC
- RKECLKIMKYLLEQLKKEFQELDAFCSYHVKTAIFHMWTQDPQDSQWDPR
- NLSSCFDKLLAFFLECLRTEKLDHYFIPKFNLFSQELIDRKSKEFLSKKI
- EYERNNGFPIFDKL
- (SEQ ID NO:
- 4)
- (M)EDPRRRTTAPRAKKPSAKRAPTQPSRTRAHAESCGPQRGARSRRAER
- DGDTTEKPRAPGPRVHPARATELTKDAQPSAMDAAGATARPAVRVPQQQA
- ILDPELPAVREPQPPADPEARKVVRGPSHRRGARSTGQPRAPRGSRKEPD
- KLKKVLDKLRLKRKDISEAAETVNKVVERLLRRMQKRESEFKGVEQLNTG
- SYYEHVKISAPNEFDVMFKLEVPRIELQEYYETGAFYLVKFKRIPRGNPL
- SHFLEGEVLSATKMLSKFRKIIKEEVKEIKDIDVSVEKEKPGSPAVTLLI
- RNPEEISVDIILALESKGSWPISTKEGLPIQGWLGTKVRTNLRREPFYLV
- PKNAKDGNSFQGETWRLSFSHTEKYILNNHGIEKTCCESSGAKCCRKECL
- KMKYLLEQLKKEFQELDAFCSYHVKTAIFHMWTQDPQDSQWDPRNLSSCF
- DKLLAFFLECLRTEKLDHYFIPKENLFSQELIDRKSKEFLSKKIEYERNN
- GFPIFDKL
- wherein the polypeptide is a constitutively active Cyclic GMP-AMP Synthase (cGAS) mutant;
- wherein residues in parentheses are optional and may be present or absent;
- wherein relative to residue numbering in SEQ ID NO:3:
- residue 53 is G, residue 54 is S, residue 57 is E, residue 66 is E, and residue 68 is D;
- and
- wherein one or both of the following are true:
- (a) residue 15 is P and residue 16 is A;
- or residue 15 is D and residue 16 is P;
- and
- (b) residue 51 is P, L, or F and residue 55 is F, I, W, or L.
30 more elements
-20. (canceled)
-28. (canceled)
Dependencies are inferred from the claim text.