[미국특허]
Delivering functional nucleic acids to mammalian cells via bacterially-derived, intact minicells
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
C07H-021/02
C07H-021/04
C12N-015/63
출원번호
US-0211098
(2005-08-25)
등록번호
US-8691963
(2014-04-08)
발명자
/ 주소
Brahmbhatt, Himanshu
MacDiarmid, Jennifer
출원인 / 주소
Engeneic Molecular Delivery Pty. Ltd.
대리인 / 주소
Foley & Lardner LLP
인용정보
피인용 횟수 :
44인용 특허 :
20
초록▼
Intact bacterially derived minicells containing functional nucleic acids or plasmids encoding functional nucleic acids can reduce, in targeted mammalian cells, drug resistance, apoptosis resistance, and neoplasticity, respectively. Methodology that employs minicells to deliver functional nucleic aci
Intact bacterially derived minicells containing functional nucleic acids or plasmids encoding functional nucleic acids can reduce, in targeted mammalian cells, drug resistance, apoptosis resistance, and neoplasticity, respectively. Methodology that employs minicells to deliver functional nucleic acids, targeting the transcripts of proteins that contribute to drug resistance or apoptosis resistance, inter alia, can be combined with chemotherapy to increase the effectiveness of the chemotherapy.
대표청구항▼
1. A composition comprising (a) a first intact, bacterially derived minicell that contains a functional nucleic acid molecule or a plasmid comprising a segment that encodes a functional nucleic acid molecule, (b) a second intact, bacterially derived minicell that is separate from said first minicell
1. A composition comprising (a) a first intact, bacterially derived minicell that contains a functional nucleic acid molecule or a plasmid comprising a segment that encodes a functional nucleic acid molecule, (b) a second intact, bacterially derived minicell that is separate from said first minicell and that contains a cancer chemotherapy agent, and (c) a pharmaceutically acceptable carrier for each of (a) and (b), wherein said functional nucleic acid molecule targets a transcript encoding a protein that contributes to resistance to said cancer chemotherapy agent in tumor cells. 2. The composition of claim 1, wherein said plasmid comprises a regulatory element operably linked to the segment that encodes a functional nucleic acid. 3. The composition of claim 2, wherein said regulatory element is a promoter dependent on RNA polymerase. 4. The composition of claim 3, wherein said promoter is the RNA polymerase III promoter H1 or U6 or 7SK or the RNA polymerase II promoter CMV immediate early promoter. 5. The composition of claim 1, wherein said functional nucleic acid is an siRNA, shRNA or miRNA molecule. 6. The composition of claim 1, wherein said functional nucleic acid is an antisense molecule. 7. The composition of claim 1, wherein said functional nucleic acid molecule is a ribozyme. 8. The composition of claim 1, wherein said functional nucleic acid molecule targets the transcript of P-glycoprotein, MDR-2 or MDR-3. 9. The composition of claim 1, wherein said functional nucleic acid molecule targets the transcript of MRP2, BCR-ABL, STI-571 resistance-associated protein, lung resistance-related protein, cyclooxygenase-2, nuclear factor kappa, XRCC1, ERCC1, GSTP1, mutant β-tubulin, or a growth factor. 10. The composition of claim 1, wherein said plasmid encodes multiple functional nucleic acid molecules. 11. The composition of claim 10, wherein said plasmid further comprises a promoter for each encoded functional nucleic acid molecule. 12. The composition of claim 1, further comprising a bispecific ligand. 13. The composition of claim 12, wherein said bispecific ligand comprises a first arm that carries specificity for a minicell surface structure and a second arm that carries specificity for a non-phagocytic mammalian cell surface receptor. 14. The composition of claim 13, wherein said minicell surface structure is an O-polysaccharide component of a lipopolysaccharide on said minicell surface. 15. The composition of claim 13, wherein said mammalian cell surface receptor is capable of activating receptor-mediated endocytosis of said minicell. 16. The composition of claim 12, wherein said bispecific ligand comprises an antibody or antibody fragment. 17. The composition of claim 1, wherein said composition contains fewer than about 1 contaminating parent bacterial cell per 107 minicells. 18. The composition of claim 1, wherein said composition contains fewer than about 1 contaminating parent bacterial cell per 108 minicells. 19. The composition of claim 1, wherein said composition contains fewer than about 1 contaminating parent bacterial cell per 109 minicells. 20. The composition of claim 1, wherein said composition contains fewer than about 1 contaminating parent bacterial cell per 1010 minicells. 21. The composition of claim 1, wherein said composition contains fewer than about 1 contaminating parent bacterial cell per 1011 minicells.
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Bancel, Stephane; Chakraborty, Tirtha; de Fougerolles, Antonin; Elbashir, Sayda M.; John, Matthias; Roy, Atanu; Whoriskey, Susan; Wood, Kristy M.; Hatala, Paul; Schrum, Jason P.; Ejebe, Kenechi; Ellsworth, Jeff Lynn; Guild, Justin, Modified polynucleotides for the production of biologics and proteins associated with human disease.
Bancel, Stephane; Chakraborty, Tirtha; de Fougerolles, Antonin; Elbashir, Sayda M.; John, Matthias; Roy, Atanu; Whoriskey, Susan; Wood, Kristy M.; Hatala, Paul; Schrum, Jason P.; Ejebe, Kenechi; Ellsworth, Jeff Lynn; Guild, Justin, Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins.
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Bancel, Stephane; Chakraborty, Tirtha; de Fougerolles, Antonin; Elbashir, Sayda M.; Ellsworth, Jeff Lynn; Ejebe, Kenechi; Guild, Justin; John, Matthias; Hatala, Paul; Roy, Atanu; Schrum, Jason P.; Whoriskey, Susan; Wood, Kristy M., Modified polynucleotides for the production of proteins.
Bancel, Stephane; Chakraborty, Tirtha; de Fougerolles, Antonin; Elbashir, Sayda M.; John, Matthias; Roy, Atanu; Whoriskey, Susan; Wood, Kristy M.; Hatala, Paul; Schrum, Jason P.; Ejebe, Kenechi; Ellsworth, Jeff Lynn; Guild, Justin, Modified polynucleotides for the production of proteins.
Bancel, Stephane; Chakraborty, Tirtha; de Fougerolles, Antonin; Elbashir, Sayda M.; John, Matthias; Roy, Atanu; Whoriskey, Susan; Wood, Kristy M.; Hatala, Paul; Schrum, Jason P.; Ejebe, Kenechi; Ellsworth, Jeff Lynn; Guild, Justin, Modified polynucleotides for the production of proteins associated with human disease.
Bancel, Stephane; Chakraborty, Tirtha; de Fougerolles, Antonin; Elbashir, Sayda M.; John, Matthias; Roy, Atanu; Whoriskey, Susan; Wood, Kristy M.; Hatala, Paul; Schrum, Jason P.; Ejebe, Kenechi; Ellsworth, Jeff Lynn; Guild, Justin, Modified polynucleotides for the production of secreted proteins.
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