Expression system for modulating an immune response
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
C12N-015/79
A61K-039/145
A61K-039/245
A61K-039/29
C07K-014/005
C12N-015/67
C40B-040/08
C40B-050/04
A61K-039/12
A61K-039/00
출원번호
US-0738284
(2008-10-02)
등록번호
US-9593340
(2017-03-14)
국제출원번호
PCT/AU2008/001463
(2008-10-02)
§371/§102 date
20101014
(20101014)
국제공개번호
WO2009/049350
(2009-04-23)
발명자
/ 주소
Frazer, Ian Hector
Dutton, Julie Louise
출원인 / 주소
Admedus Vaccines Pty Ltd.
대리인 / 주소
Cooley LLP
인용정보
피인용 횟수 :
0인용 특허 :
57
초록▼
The present invention discloses methods and compositions for modulating the quality of an immune response to a target antigen in a mammal, which response results from the expression of a polynucleotide that encodes at least a portion of the target antigen, wherein the quality is modulated by replaci
The present invention discloses methods and compositions for modulating the quality of an immune response to a target antigen in a mammal, which response results from the expression of a polynucleotide that encodes at least a portion of the target antigen, wherein the quality is modulated by replacing at least one codon of the polynucleotide with a synonymous codon that has a higher or lower preference of usage by the mammal to confer the immune response than the codon it replaces.
대표청구항▼
1. A method for constructing a synthetic polynucleotide from which a polypeptide is producible to confer a stronger or enhanced immune response to a target antigen in a mammal than that conferred by a parent polynucleotide that encodes the same polypeptide, wherein the immune response is selected fr
1. A method for constructing a synthetic polynucleotide from which a polypeptide is producible to confer a stronger or enhanced immune response to a target antigen in a mammal than that conferred by a parent polynucleotide that encodes the same polypeptide, wherein the immune response is selected from the group consisting of (1) a humoral immune response, (2) a cellular immune response and (3) a cellular immune response and a humoral immune response, wherein the polypeptide corresponds to at least a portion of the target antigen, the method comprising constructing the synthetic polynucleotide so that it is distinguished from the parent polynucleotide by replacement of at least 5% of codons which correspond to the target antigen in the parent polynucleotide with synonymous codons, wherein individual codon replacements are carried out by: (a) selecting a first codon of the parent polynucleotide for replacement with a synonymous codon according to TABLE 3: TABLE 3First CodonSynonymous CodonAlaGCGAlaGCTAlaGCAAlaGCTAlaGCCAlaGCTArgCGGArgCGAArgCGGArgCGTArgCGGArgAGAArgAGGArgCGAArgAGGArgCGTArgAGGArgAGAGluGAGGluGAAGlyGGCGlyGGAGlyGGTGlyGGAGlyGGGGlyGGALeuTTALeuCTALeuTTALeuCTTLeuTTALeuTTGLeuTTGLeuCTALeuTTGLeuCTTPheTTCPheTTTProCCGProCCTProCCAProCCTSerAGTSerTCGSerAGTSerTCTSerAGTSerTCASerAGCSerTCGSerAGCSerTCTSerAGCSerTCASerAGCSerTCCSerTCCSerTCGSerTCASerTCGSerTCTSerTCGThrACTThrACGThrACTThrACAThrACAThrACGThrACCThrACGValGTAValGTTand (b) replacing the first codon with the synonymous codon. 2. The method according to claim 1, further comprising (i) selecting a second codon of the parent polynucleotide for replacement with a synonymous codon, wherein the synonymous codon is selected on the basis that it exhibits a higher immune response preference than the second codon in a comparison of immune response preferences; and (ii) replacing the second codon with the synonymous codon, wherein the comparison of immune response preferences of the codons is represented by TABLE 4: Second CodonSynonymous CodonAlaGCGAlaGCTAlaGCGAlaGCCAlaGCAAlaGCTAlaGCAAlaGCCAlaGCCAlaGCTArgCGGArgCGAArgCGGArgCGCArgCGGArgCGTArgCGGArgAGAArgAGGArgCGAArgAGGArgCGCArgAGGArgCGTArgAGGArgAGAAsnAATAsnAACAspGATAspGACCysTGTCysTGCGluGAGGluGAAGlyGGCGlyGGAGlyGGTGlyGGAGlyGGGGlyGGAIleATAIleATCIleATAIleATTIleATTIleATCLeuTTALeuCTGLeuTTALeuCTCLeuTTALeuCTALeuTTALeuCTTLeuTTALeuTTGLeuTTGLeuCTGLeuTTGLeuCTCLeuTTGLeuCTALeuTTGLeuCTTLeuCTTLeuCTGLeuCTTLeuCTCLeuCTALeuCTGLeuCTALeuCTCPheTTCPheTTTProCCGProCCCProCCGProCCTProCCAProCCCProCCAProCCTProCCTProCCCSerAGTSerTCGSerAGTSerTCTSerAGTSerTCASerAGTSerTCCSerAGCSerTCGSerAGCSerTCTSerAGCSerTCASerAGCSerTCCSerTCCSerTCGSerTCASerTCGSerTCTSerTCGThrACTThrACGThrACTThrACCThrACTThrACAThrACAThrACGThrACAThrACCThrACCThrACGTyrTATTyrTACValGTAValGTGValGTAValGTCValGTAValGTTValGTTValGTGValGTTValGTC. 3. A method for constructing a synthetic polynucleotide from which a polypeptide is producible to confer a weaker or reduced immune response to a target antigen in a mammal than that conferred by a parent polynucleotide that encodes the same polypeptide, wherein the immune response is selected from the group consisting of (1) a humoral immune response; (2) a cellular immune response; and (3) a cellular immune response and a humoral immune response, wherein the polypeptide corresponds to at least a portion of the target antigen, the method comprising constructing the synthetic polynucleotide so that it is distinguished from the parent polynucleotide by replacement of at least 5% of codons, wherein individual codon replacements are carried out by: (a) selecting a first codon of the parent polynucleotide for replacement with a synonymous codon; and (b) replacing the first codon with the synonymous codon to construct the synthetic polynucleotide, wherein the first and synonymous codons are selected from the TABLE 5: First CodonSynonymous CodonAlaGCTAlaGCGAlaGCTAlaGCAAlaGCTAlaGCCAlaGCCAlaGCGAlaGCCAlaGCAArgCGAArgAGGArgCGAArgCGGArgCGCArgAGGArgCGCArgCGGArgCGTArgAGGArgCGTArgCGGArgAGAArgAGGArgAGAArgCGGAsnAACAsnAATAspGACAspGATCysTGCCysTGTGluGAAGluGAGGlyGGAGlyGGCGlyGGAGlyGGTGlyGGAGlyGGGIleATCIleATAIleATCIleATTIleATTIleATALeuCTGLeuCTALeuCTGLeuCTTLeuCTGLeuTTGLeuCTGLeuTTALeuCTCLeuCTALeuCTCLeuCTTLeuCTCLeuTTGLeuCTCLeuTTALeuCTALeuTTGLeuCTALeuTTALeuCTTLeuTTGLeuCTTLeuTTALeuTTGLeuTTAPheTTTPheTTCProCCCProCCTProCCCProCCAProCCCProCCGProCCTProCCAProCCTProCCGSerTCGSerTCTSerTCGSerTCASerTCGSerTCCSerTCGSerAGCSerTCGSerAGTSerTCTSerAGCSerTCTSerAGTSerTCASerAGCSerTCASerAGTSerTCCSerAGCSerTCCSerAGTThrACGThrACCThrACGThrACAThrACGThrACTThrACCThrACAThrACCThrACTThrACAThrACTTyrTACTyrTATValGTGValGTTValGTGValGTAValGTCValGTTValGTCValGTAValGTTValGTA. 4. A method for constructing a synthetic polynucleotide from which a polypeptide is producible to confer a weaker or reduced immune response to a target antigen in a mammal than that conferred by a parent polynucleotide that encodes the same polypeptide, wherein the immune response is selected from the group consisting of (1) a humoral immune response; (2) a cellular immune response; and (3) a cellular immune response and a humoral immune response, wherein the polypeptide corresponds to at least a portion of the target antigen, the method comprising constructing the synthetic polynucleotide so that it is distinguished from the parent polynucleotide by replacement of at least 5% of codons, wherein individual codon replacements are carried out by: (a) selecting a first codon of the parent polynucleotide for replacement with a synonymous codon; and (b) replacing the first codon with the synonymous codon to construct the synthetic polynucleotide, wherein the first and synonymous codons are selected from TABLE 6: First CodonSynonymous CodonAlaGCTAlaGCGAlaGCTAlaGCAAlaGCTAlaGCCArgCGAArgAGGArgCGAArgCGGArgCGTArgAGGArgCGTArgCGGArgAGAArgAGGArgAGAArgCGGGluGAAGluGAGGlyGGAGlyGGCGlyGGAGlyGGTGlyGGAGlyGGGLeuCTALeuTTGLeuCTALeuTTALeuCTTLeuTTGLeuCTTLeuTTALeuTTGLeuTTAPheTTTPheTTCProCCTProCCAProCCTProCCGSerTCGSerTCTSerTCGSerTCASerTCGSerTCCSerTCGSerAGCSerTCGSerAGTSerTCTSerAGCSerTCTSerAGTSerTCASerAGCSerTCASerAGTSerTCCSerAGCThrACGThrACCThrACGThrACAThrACGThrACTThrACAThrACTValGTTValGTA. 5. The method according to claim 4, further comprising (i) selecting a second codon of the parent polynucleotide for replacement with a synonymous codon, wherein the synonymous codon is selected on the basis that it exhibits a lower immune response preference than the second codon in a comparison of immune response preferences; and; (ii) replacing the second codon with the synonymous codon, wherein the comparison of immune response preferences of the codons is represented by TABLE 7: TABLE 7Second CodonSynonymous CodonAlaGCTAlaGCGAlaGCTAlaGCAAlaGCTAlaGCCAlaGCCAlaGCGAlaGCCAlaGCAArgCGAArgAGGArgCGAArgCGGArgCGCArgAGGArgCGCArgCGGArgCGTArgAGGArgCGTArgCGGArgAGAArgAGGArgAGAArgCGGAsnAACAsnAATAspGACAspGATCysTGCCysTGTGluGAAGluGAGGlyGGAGlyGGCGlyGGAGlyGGTGlyGGAGlyGGGIleATCIleATAIleATCIleATTIleATTIleATALeuCTGLeuCTALeuCTGLeuCTTLeuCTGLeuTTGLeuCTGLeuTTALeuCTCLeuCTALeuCTCLeuCTTLeuCTCLeuTTGLeuCTCLeuTTALeuCTALeuTTGLeuCTALeuTTALeuCTTLeuTTGLeuCTTLeuTTALeuTTGLeuTTAPheTTTPheTTCProCCCProCCTProCCCProCCAProCCCProCCGProCCTProCCAProCCTProCCGSerTCGSerTCTSerTCGSerTCASerTCGSerTCCSerTCGSerAGCSerTCGSerAGTSerTCTSerAGCSerTCTSerAGTSerTCASerAGCSerTCASerAGTSerTCCSerAGCSerTCCSerAGTThrACGThrACCThrACGThrACAThrACGThrACTThrACCThrACAThrACCThrACTThrACAThrACTTyrTACTyrTATValGTGValGTTValGTGValGTAValGTCValGTTValGTCValGTAValGTTValGTA. 6. A method of making a chimeric construct, comprising constructing a synthetic polynucleotide according to the method of claim 1 and operably linking a regulatory polynucleotide to the synthetic polynucleotide. 7. The method according to claim 6, further comprising constructing the chimeric construct so that it includes the coding sequence of an adjuvant. 8. The method according to claim 7, wherein the adjuvant is selected from: detoxified mutants of bacterial ADP-ribosylating toxins, diphtheria toxin, pertussis toxin, cholera toxin, Escherichia coli heat-labile toxins, Pseudomonas endotoxin A, Clostridium botulinum C2 and C3 toxins, toxins from C. perfringens, C. spiriforma and C. difficile; and protein-destabilizing elements. 9. The method according to claim 7, wherein the adjuvant is a protein-destabilizing element selected from a destabilizing amino acid at the amino-terminus of the polypeptide, a PEST region or an ubiquitin. 10. The method according to claim 6, further comprising formulating the chimeric construct for transcutaneous administration, epidermal administration, dermal administration, intradermal administration, biolistic delivery, microneedle delivery or intradermal injection. 11. A synthetic polynucleotide comprising the nucleic acid sequence set forth in SEQ ID NO: 82. 12. A chimeric construct comprising the synthetic polynucleotide of claim 11 operably linked to a regulatory polynucleotide. 13. The method of claim 1, wherein the target antigen is a herpes simplex virus antigen. 14. The method of claim 13, wherein the herpes simplex virus antigen is a glycoprotein D. 15. The method of claim 13, wherein the herpes simplex virus antigen is gD2.
연구과제 타임라인
LOADING...
LOADING...
LOADING...
LOADING...
LOADING...
이 특허에 인용된 특허 (57)
Russell David W. ; Rutledge Elizabeth A., Adeno-associated virus (AAV) isolates and AAV vectors derived therefrom.
Kurtzman Gary J. ; Colosi Peter C. ; Yoshida Jun,JPX ; Mizuno Masaaki,JPX ; Okada Hideho, Adeno-associated virus vectors comprising a first and second nucleic acid sequence.
Graham Frank L.,CAX ; Anton Martina,CAX ; Bacchetti Silvia,CAX ; Wang Ping,CAX ; Rudnicki Michael A.,CAX ; Muller William J.,CAX, Adenoviruses for control of gene expression.
Dubensky ; Jr. Thomas W. ; Polo John M. ; Ibanez Carlos E. ; Chang Stephen M. W. ; Jolly Douglas J. ; Driver David A., Alphavirus structural protein expression cassettes.
Dubensky ; Jr. Thomas W. ; Polo John M. ; Ibanez Carlos E. ; Chang Stephen M. W. ; Jolly Douglas J. ; Driver David A. ; Belli Barbara A., Alphavirus vector constructs.
Sanford John C. (Geneva NY) Wolf Edward D. (Ithaca NY) Allen Nelson K. (Newfield NY), Apparatus for transporting substances into living cells and tissues.
Sanford John C. (Geneva NY) Wolf Edward D. (Ithaca NY) Allen Nelson K. (Newfield NY), Biolistic apparatus for delivering substances into cells and tissues in a non-lethal manner.
Woo Savio L. C. (5343 Rutherglenn Houston TX 77096) Nordloh Peter W. (1104 S. 8th St. Burlington IA 52601) Stenlund Arne (1 Bungtown Rd. Cold Spring Harbor NY 11724), Episomal vector systems and related methods.
Alexander Ian E. (Brier WA) Russell David W. (Seattle WA) Miller A. Dusty (Seattle WA), Method for increasing transduction of cells by adeno-associated virus vectors.
Sanford John C. (Geneva NY) Wolf Edward D. (Ithaca NY) Allen Nelson K. (Newfield NY), Method for transporting substances into living cells and tissues.
Sanford John C. (Geneva NY) Wolf Edward D. (Ithaca NY) Allen Nelson K. (Newfield NY), Method for transporting substances into living cells and tissues and apparatus therefor.
Sanford John C. (Geneva NY) Wolf Edward D. (Ithaca NY) Allen Nelson K. (Newfield NY), Method for transporting substances into living cells and tissues and apparatus therefor.
Varshavsky Alexander J. (Boston MA) Johnson Erica S. (Somerville MA) Gonda David K. (Quincy MA) Hochstrasser Mark (Somerville MA), Methods for trans-destabilization of specific proteins in vivo and DNA molecules useful therefor.
Bachmair Andreas (Cologne MA DEX) Finley Daniel (Cambridge MA) Varshavsky Alexander (Boston MA), Methods of generating desired amino-terminal residues in proteins.
McKinnon ; Jr. Charles N. (Laguna Niguel CA) Peterson Steven F. (West Linn OR) Smith Paul E. (Tualatin OR) Nakagawa Takaaki (Tigard OR) Bartholomew Victor L. (Tigard OR), Needleless hypodermic injection device.
Peterson Steven F. (West Linn OR) McKinnon ; Jr. Charles N. (Laguna Niguel CA) Smith Paul E. (Tualatin OR) Nakagawa Takaaki (Tigard OR) Bartholomew Victor L. (Tigard OR), Needleless hypodermic injection methods and device.
Peterson Steven F. (West Linn OR) McKinnon ; Jr. Charles N. (Laguna Niguel CA) Smith Paul E. (Tualatin OR) Nakagawa Takaaki (Tigard OR) Bartholomew Victor L. (Tigard OR), Needleless hypodermic injection methods and device.
Haynes Joel,CAX ; Klein Michel Henri,CAX ; Rovinski Benjamin,CAX ; Cao Shi Xian,CAX, Non-infectious, replication-impaired, immunogenic human immunodeficiency virus type 1 retrovirus-like particles with mul.
Wu Ray J. (Ithaca NY) Bahl Chander P. (Concord CA) Narang Saran A. (Ottawa CAX), Oligonucleotides useful as adaptors in DNA cloning, adapted DNA molecules, and methods of preparing adaptors and adapted.
Dorner Friedrich (Vienna ATX) Scriba Marianne (Maria Enzerdorf ATX) Weil Rudolf (Vienna ATX), Process for producing a structurally modified interferon.
Hock Lisa J. (La Jolla CA) Cochran Mark D. (Carlsbad CA) Macdonald Richard D. (San Diego CA), Recombinant human cytomegalovirus containing foreign gene.
※ AI-Helper는 부적절한 답변을 할 수 있습니다.