KR950703650A - TRANSLOCATION SIGNAL FACILITATED NUCLEAR DELIVERY OF MACROMOLECULES - Google Patents

TRANSLOCATION SIGNAL FACILITATED NUCLEAR DELIVERY OF MACROMOLECULES Download PDF

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KR950703650A
KR950703650A KR1019950700814A KR19950700814A KR950703650A KR 950703650 A KR950703650 A KR 950703650A KR 1019950700814 A KR1019950700814 A KR 1019950700814A KR 19950700814 A KR19950700814 A KR 19950700814A KR 950703650 A KR950703650 A KR 950703650A
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polypeptide
composition
binding
macromolecule
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KR1019950700814A
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알. 바르네트 토마스
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유진 시모낼리
베이어 코포레이션
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
    • C07K14/21—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Pseudomonadaceae (F)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/6415—Toxins or lectins, e.g. clostridial toxins or Pseudomonas exotoxins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/09—Fusion polypeptide containing a localisation/targetting motif containing a nuclear localisation signal
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/55—Fusion polypeptide containing a fusion with a toxin, e.g. diphteria toxin

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • General Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Zoology (AREA)
  • Biomedical Technology (AREA)
  • Wood Science & Technology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicinal Chemistry (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Microbiology (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Toxicology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Peptides Or Proteins (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Formation Of Insulating Films (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

본 발명은 신규한 수용-매개 전달 시스템에 의해 핵으로 뉴클레오티드 서열 또는 단백질로 도입하는 방법에 관한 것이다. 전달 시스템은 세포-수용체-결합 도메인, 세포질 전좌 도메인 및 핵 전좌 신호 도메인을 포함한다. 이러한 시스템은 일단 핵으로 흡수되는 작용을 하는 거대분자를 전달할 수 있다.The present invention is directed to a method of introducing a nucleotide sequence or protein into the nucleus by a novel acceptor-mediated delivery system. The delivery system includes a cell-receptor-binding domain, a cytoplasmic translocation domain and a nuclear translocation signal domain. Such a system can deliver macromolecules that act once absorbed into the nucleus.

Description

마크로 분자의 전좌 신호 촉진 핵 전달방법(TRANSLOCATION SIGNAL FACILITATED NUCLEAR DELIVERY OF MACROMOLECULES)TRANSLOCATION SIGNAL FACILITATED NUCLEAR DELIVERY OF MACROMOLECULES

본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음Since this is an open matter, no full text was included.

제1도 내지 제7도는 각각 본 발명에 따라 세폭핵 내로 이종물질을 도입시키는 방법을 나타내는 도면이다.1 to 7 are diagrams showing a method for introducing heterogeneous materials into narrow nuclei according to the present invention, respectively.

Claims (8)

수용체-결합 도메인, 세포질 전좌 도메인, 핵 전좌 도메인을 포함하는 폴리펩티드, 및 선택된 거대분자를 상기 폴리펩티드에 결합시키는 수단으로 이루어지는 조성물.A composition comprising a receptor-binding domain, a cytoplasmic translocation domain, a polypeptide comprising a nuclear translocation domain, and means for binding a selected macromolecule to said polypeptide. 제1항에 있어서, 상기 거대분자가 뉴클레오티드, 올리고펩티드, 폴리펩티드 및 단백질로 이루어진 군으로부터 선택되며, 이것들은 각각 인자 Ⅷ을 코드화하는 뉴클레오티드 서열, 알파-1-안티트립신을 코드화 하는 뉴클레오티드 서열, 유전자 발현의 조절자인 폴리펩티드, 베타 갈라토시다아제인 것을 특징으로 하는 조성물.The method according to claim 1, wherein the macromolecule is selected from the group consisting of nucleotides, oligopeptides, polypeptides and proteins, each of which is a nucleotide sequence encoding factor VII, a nucleotide sequence encoding alpha-1-antitrypsin, gene expression Polypeptide is a modulator of beta galactosidase, characterized in that the composition. 제1항에 있어서, 상기 수용체-결합 도메인이 특정 세포 수용체에 대한 독소-유도 리간드이며, 디프테리아 독소 또는 슈도모나스 외독소 A로부터 유도되는 것을 특징으로 하는 조성물.2. The composition of claim 1, wherein said receptor-binding domain is a toxin-inducing ligand for a particular cellular receptor and is derived from diphtheria toxin or Pseudomonas exotoxin A. 3. 제1항에 있어서, 상기 세포질 전좌 도메인이 슈도모나스 외독소 A로부터 유도되는 것을 특징으로 하는 조성물.2. The composition of claim 1, wherein said cytoplasmic translocation domain is derived from Pseudomonas exotoxin A. 제1항에 있어서, 상기 핵 전좌 신호 도메인이 SV40 핵산 서열, 이스트 알파-2 핵산 서열 및 GAL-4 핵산 서열로 이루어진 군에서 선택되는 것을 특징으로 하는 조성물.The composition of claim 1, wherein the nuclear translocation signal domain is selected from the group consisting of an SV40 nucleic acid sequence, an yeast alpha-2 nucleic acid sequence, and a GAL-4 nucleic acid sequence. 제1항에 있어서, 핵 전좌 도메인에 거대분자를 결합시키는 수단이 폴리-L-리신, 폴리-D-리신, 폴리 NTS, 오르니틴, 푸트레신, 히스톤, GAL4, 호메 오복스 도메인, 스페르미딘 및 스페르민으로 이루어진 군에서 선택되는 다가 양이 온성 거대 분자인 것을 특징으로 하는 조성물.The method of claim 1, wherein the means for binding the macromolecules to the nuclear translocation domain is poly-L-lysine, poly-D-lysine, poly NTS, ornithine, putrescine, histone, GAL4, homeobox domain, spermi A polyvalent amount is a ionic macromolecule selected from the group consisting of dean and spermine. 표적 세포의 핵 내에 외인성 거대분자를 삽입하는 방법으로서, (a) 수용체-결합 도메인, 세포질 전좌 도메인, 핵 전좌 도메인, 및 선택된 거대분자를 상기 폴리펩티드에 결합시키는 수단으로 이루어진 폴리펩티드를 표적 세포에 투여하는 단계, (b) 상기 폴리펩티드를 기진 세포를 인큐베이션 시키는 단계, 및 (c) 검정방법에 의해 전달을 결정하는 단계로 이루어지는 방법.A method of inserting an exogenous macromolecule into a nucleus of a target cell, the method comprising: (a) administering to a target cell a polypeptide comprising a receptor-binding domain, a cytoplasmic translocation domain, a nuclear translocation domain, and a means for binding the selected macromolecule to the polypeptide (B) incubating the polypeptide with the viable cell, and (c) determining delivery by assay. 제7항에 있어서, 폴리펩티드가 제2항, 3항 4항 5항 또는 6항에 기재된 바와같은 것을 특징으로 하는 조성물.8. A composition according to claim 7, wherein the polypeptide is as described in claims 2, 3, 4, 5 or 6. ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.※ Note: The disclosure is based on the initial application.
KR1019950700814A 1992-08-25 1993-08-24 TRANSLOCATION SIGNAL FACILITATED NUCLEAR DELIVERY OF MACROMOLECULES KR950703650A (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US93507492A 1992-08-25 1992-08-25
US07/935074 1992-08-25
PCT/US1993/007945 WO1994004696A1 (en) 1992-08-25 1993-08-24 Translocation signal facilitated nuclear delivery of macromolecules

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KR950703650A true KR950703650A (en) 1995-09-20

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EP (1) EP0658210A1 (en)
JP (1) JPH08504565A (en)
KR (1) KR950703650A (en)
AU (1) AU674026B2 (en)
CA (1) CA2143308A1 (en)
FI (1) FI950866A (en)
IL (1) IL106760A (en)
NZ (1) NZ255870A (en)
WO (1) WO1994004696A1 (en)
ZA (1) ZA936189B (en)

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US9085638B2 (en) 2007-03-07 2015-07-21 The Johns Hopkins University DNA vaccine enhancement with MHC class II activators
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CA2131620A1 (en) * 1992-03-20 1993-09-30 Louis C. Smith A dna transporter system and method of use

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AU674026B2 (en) 1996-12-05
FI950866A0 (en) 1995-02-24
JPH08504565A (en) 1996-05-21
ZA936189B (en) 1995-01-10
WO1994004696A1 (en) 1994-03-03
AU5088593A (en) 1994-03-15
NZ255870A (en) 1996-09-25
EP0658210A1 (en) 1995-06-21
CA2143308A1 (en) 1994-03-03
IL106760A0 (en) 1993-12-08
IL106760A (en) 1999-12-31
FI950866A (en) 1995-04-24

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