메뉴 건너뛰기




Volumn 1, Issue 2, 1999, Pages 244-251

Non-viral amplification systems for gene transfer: Vectors based on alphaviruses

Author keywords

[No Author keywords available]

Indexed keywords

ANTIGEN; DNA; DNA VACCINE; RNA; RNA POLYMERASE; VIRUS VECTOR;

EID: 0032965983     PISSN: 14648431     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article
Times cited : (52)

References (53)
  • 1
    • 0030753522 scopus 로고    scopus 로고
    • DNA for genetic vaccination and therapy
    • Moelling K: DNA for genetic vaccination and therapy. Cytokines Cell Mol Ther (1997) 3:127-135.
    • (1997) Cytokines Cell Mol Ther , vol.3 , pp. 127-135
    • Moelling, K.1
  • 2
    • 0030811634 scopus 로고    scopus 로고
    • Nucleic acid vaccines: An overview
    • Robinson HL: Nucleic acid vaccines: an overview. Vaccine (1997) 15:785-787.
    • (1997) Vaccine , vol.15 , pp. 785-787
    • Robinson, H.L.1
  • 4
    • 0013686942 scopus 로고    scopus 로고
    • In vitro transfection with intravascular delivered DNA
    • Herweijer H, Wolff H: In vitro transfection with intravascular delivered DNA. Curr Res Mol Ther (1998) 1:504-509.
    • (1998) Curr Res Mol Ther , vol.1 , pp. 504-509
    • Herweijer, H.1    Wolff, H.2
  • 6
    • 14744304517 scopus 로고
    • A new generation of animal cell expression vectors based on the Semliki Forest virus replicon
    • Liljeström P, Garoff H: A new generation of animal cell expression vectors based on the Semliki Forest virus replicon. Biotechnology (1991) 9:1356-1361.
    • (1991) Biotechnology , vol.9 , pp. 1356-1361
    • Liljeström, P.1    Garoff, H.2
  • 7
    • 0031583842 scopus 로고    scopus 로고
    • Replicon-helper systems from attenuated Venezuelan equine encephalitis virus - Expression of heterologous genes in vitro and immunization against heterologous pathogens in vivo
    • Pushko P, Parker M, Ludwig GV, Davis NL, Johnston RE, Smith JF: Replicon-helper systems from attenuated Venezuelan equine encephalitis virus - Expression of heterologous genes in vitro and immunization against heterologous pathogens in vivo. Virology (1997) 239:389-401.
    • (1997) Virology , vol.239 , pp. 389-401
    • Pushko, P.1    Parker, M.2    Ludwig, G.V.3    Davis, N.L.4    Johnston, R.E.5    Smith, J.F.6
  • 8
    • 0024514346 scopus 로고
    • Sindbis virus: An efficient, broad host range vector for gene expression in animal cells
    • Xiong C, Levis R, Shen P, Schlesinger S, Rice CM, Huang HV: Sindbis virus: an efficient, broad host range vector for gene expression in animal cells. Science (1989) 243:1188-1191.
    • (1989) Science , vol.243 , pp. 1188-1191
    • Xiong, C.1    Levis, R.2    Shen, P.3    Schlesinger, S.4    Rice, C.M.5    Huang, H.V.6
  • 10
    • 0028027482 scopus 로고
    • Alphavirus expression systems
    • Liljeström P: Alphavirus expression systems. Curr Opin Biotechnol (1994) 5:495-500.
    • (1994) Curr Opin Biotechnol , vol.5 , pp. 495-500
    • Liljeström, P.1
  • 11
    • 0032191461 scopus 로고    scopus 로고
    • Recent advances in gene expression using alphavirus vectors
    • Garoff H, Li KJ: Recent advances in gene expression using alphavirus vectors. Curr Opin Biotechnol (1998) 9:464-469.
    • (1998) Curr Opin Biotechnol , vol.9 , pp. 464-469
    • Garoff, H.1    Li, K.J.2
  • 12
    • 0028088152 scopus 로고
    • The alphaviruses: Gene expression, replication, and evolution
    • Strauss JH, Strauss EG: The alphaviruses: gene expression, replication, and evolution. Microbiol Rev (1994) 58:491-562.
    • (1994) Microbiol Rev , vol.58 , pp. 491-562
    • Strauss, J.H.1    Strauss, E.G.2
  • 13
    • 8944255627 scopus 로고    scopus 로고
    • The translation-enhancing region of the Semliki Forest virus subgenome is only functional in the virus-infected cell
    • Sjöberg EM, Garoff H: The translation-enhancing region of the Semliki Forest virus subgenome is only functional in the virus-infected cell. J Gen Virol (1996) 77:1323-1327.
    • (1996) J Gen Virol , vol.77 , pp. 1323-1327
    • Sjöberg, E.M.1    Garoff, H.2
  • 14
    • 0028152741 scopus 로고
    • A significantly improved Semliki Forest virus expression system based on translation enhancer segments from the viral capsid gene
    • Sjöberg EM, Suomalainen M, Garoff H: A significantly improved Semliki Forest virus expression system based on translation enhancer segments from the viral capsid gene. Biotechnology (1994) 12:1127-1131.
    • (1994) Biotechnology , vol.12 , pp. 1127-1131
    • Sjöberg, E.M.1    Suomalainen, M.2    Garoff, H.3
  • 15
    • 0028171032 scopus 로고
    • Translation of Sindbis virus mRNA: Effects of sequences downstream of the initiating codon
    • Frolov I, Schlesinger S: Translation of Sindbis virus mRNA: effects of sequences downstream of the initiating codon. J Virol (1994) 68:8111-8117.
    • (1994) J Virol , vol.68 , pp. 8111-8117
    • Frolov, I.1    Schlesinger, S.2
  • 16
    • 0025912001 scopus 로고
    • In vitro mutagenesis of a full-length cDNA clone of Semliki Forest virus: The small 6,000-molecular-weight membrane protein modulates virus release
    • Liljeström P, Lusa S, Huylebroeck D, Garoff H: In vitro mutagenesis of a full-length cDNA clone of Semliki Forest virus: the small 6,000-molecular-weight membrane protein modulates virus release. J Virol (1991) 65:4107-4113.
    • (1991) J Virol , vol.65 , pp. 4107-4113
    • Liljeström, P.1    Lusa, S.2    Huylebroeck, D.3    Garoff, H.4
  • 17
    • 0023510284 scopus 로고
    • Production of infectious RNA transcripts from Sindbis virus cDNA clones: Mapping of lethal mutations, rescue of a temperature-sensitive marker, and in vitro mutagenesis to generate defined mutants
    • Rice CM, Levis R, Strauss JH, Huang HV: Production of infectious RNA transcripts from Sindbis virus cDNA clones: mapping of lethal mutations, rescue of a temperature-sensitive marker, and in vitro mutagenesis to generate defined mutants. J Virol (1987) 61:3809-3819.
    • (1987) J Virol , vol.61 , pp. 3809-3819
    • Rice, C.M.1    Levis, R.2    Strauss, J.H.3    Huang, H.V.4
  • 18
    • 0024403231 scopus 로고
    • In vitro synthesis of infectious Venezuelan equine encephalitis virus RNA from a cDNA clone: Analysis of a viable deletion mutant
    • Davis NL, Willis LV, Smith JF, Johnston RE: In vitro synthesis of infectious Venezuelan equine encephalitis virus RNA from a cDNA clone: analysis of a viable deletion mutant. Virology (1989) 171:189-204.
    • (1989) Virology , vol.171 , pp. 189-204
    • Davis, N.L.1    Willis, L.V.2    Smith, J.F.3    Johnston, R.E.4
  • 19
    • 0027421842 scopus 로고
    • Sindbis virus expression vectors: Packaging of RNA replicons by using defective helper RNAs
    • Bredenbeek PJ, Frolov I, Rice CM, Schlesinger S: Sindbis virus expression vectors: packaging of RNA replicons by using defective helper RNAs. J Virol (1993) 67:6439-6446.
    • (1993) J Virol , vol.67 , pp. 6439-6446
    • Bredenbeek, P.J.1    Frolov, I.2    Rice, C.M.3    Schlesinger, S.4
  • 20
    • 0022498060 scopus 로고
    • Deletion mapping of Sindbis virus Dl RNAs derived from cDNAs defines the sequences essential for replication and packaging
    • Levis R, Weiss BG, Tsiang M, Huang H, Schlesinger S: Deletion mapping of Sindbis virus Dl RNAs derived from cDNAs defines the sequences essential for replication and packaging. Cell (1986) 44:137-145.
    • (1986) Cell , vol.44 , pp. 137-145
    • Levis, R.1    Weiss, B.G.2    Tsiang, M.3    Huang, H.4    Schlesinger, S.5
  • 21
    • 0024428285 scopus 로고
    • Evidence for specificity in the encapsidation of Sindbis virus RNAs
    • Weiss B, Nitschko H, Ghattas I, Wright R, Schlesinger S: Evidence for specificity in the encapsidation of Sindbis virus RNAs. J Virol (1989) 63:5310-5318.
    • (1989) J Virol , vol.63 , pp. 5310-5318
    • Weiss, B.1    Nitschko, H.2    Ghattas, I.3    Wright, R.4    Schlesinger, S.5
  • 22
    • 0031977997 scopus 로고    scopus 로고
    • Deletion analysis of a defective interfering Semliki Forest virus RNA genome defines a region in the nsP2 sequence that is required for efficient packaging of the genome into virus particles
    • White CL, Thomson M, Dimmock NJ: Deletion analysis of a defective interfering Semliki Forest virus RNA genome defines a region in the nsP2 sequence that is required for efficient packaging of the genome into virus particles. J Virol (1998) 72:4320-4326.
    • (1998) J Virol , vol.72 , pp. 4320-4326
    • White, C.L.1    Thomson, M.2    Dimmock, N.J.3
  • 23
    • 0028971181 scopus 로고
    • Genesis of Sindbis virus by in vivo recombination of nonreplicative RNA precursors
    • Raju R, Subramaniam SV, Haijou M: Genesis of Sindbis virus by in vivo recombination of nonreplicative RNA precursors. J Virol (1995) 69:7391-7401.
    • (1995) J Virol , vol.69 , pp. 7391-7401
    • Raju, R.1    Subramaniam, S.V.2    Haijou, M.3
  • 24
    • 0025861666 scopus 로고
    • Recombination between Sindbis virus RNAs
    • Weiss BG, Schlesinger S: Recombination between Sindbis virus RNAs. J Virol (1991) 65:4017-4025.
    • (1991) J Virol , vol.65 , pp. 4017-4025
    • Weiss, B.G.1    Schlesinger, S.2
  • 25
    • 0029946792 scopus 로고    scopus 로고
    • Nonhomologous RNA-RNA recombination events at the 3′ nontranslated region of the Sindbis virus genome: Hot spots and utilization of nonviral sequences
    • Haijou M, Hill KR, Subramaniam SV, Hu JY, Raju R: Nonhomologous RNA-RNA recombination events at the 3′ nontranslated region of the Sindbis virus genome: hot spots and utilization of nonviral sequences. J Virol (1996) 70:5153-5164.
    • (1996) J Virol , vol.70 , pp. 5153-5164
    • Haijou, M.1    Hill, K.R.2    Subramaniam, S.V.3    Hu, J.Y.4    Raju, R.5
  • 26
    • 14744292350 scopus 로고
    • Semliki Forest virus expression system: Production of conditionally infectious recombinant particles
    • Berglund P, Sjöberg M, Garoff H, Atkins GJ, Sheahan BJ, Liljeström P: Semliki Forest virus expression system: production of conditionally infectious recombinant particles. Biotechnol (1993) 11:916-920.
    • (1993) Biotechnol , vol.11 , pp. 916-920
    • Berglund, P.1    Sjöberg, M.2    Garoff, H.3    Atkins, G.J.4    Sheahan, B.J.5    Liljeström, P.6
  • 27
    • 0032906979 scopus 로고    scopus 로고
    • Two-helper RNA system for production of recombinant Semliki forest virus particles
    • Smerdou C, Liljeström P: Two-helper RNA system for production of recombinant Semliki forest virus particles. J Virol (1999) 73:1092-1098.
    • (1999) J Virol , vol.73 , pp. 1092-1098
    • Smerdou, C.1    Liljeström, P.2
  • 28
    • 0030941093 scopus 로고    scopus 로고
    • Sindbis virus replicons and Sindbis virus: Assembly of chimeras and of particles deficient in virus RNA
    • Frolov I, Frolova E, Schlesinger S: Sindbis virus replicons and Sindbis virus: assembly of chimeras and of particles deficient in virus RNA. J Virol (1997) 71:2819-2829.
    • (1997) J Virol , vol.71 , pp. 2819-2829
    • Frolov, I.1    Frolova, E.2    Schlesinger, S.3
  • 31
    • 0028057720 scopus 로고
    • Comparison of the effects of Sindbis virus and Sindbis virus replicons on host cell protein synthesis and cytopathogenicity in BHK cells
    • Frolov I, Schlesinger S: Comparison of the effects of Sindbis virus and Sindbis virus replicons on host cell protein synthesis and cytopathogenicity in BHK cells. J Virol (1994) 68:1721-1727.
    • (1994) J Virol , vol.68 , pp. 1721-1727
    • Frolov, I.1    Schlesinger, S.2
  • 33
    • 0032505567 scopus 로고    scopus 로고
    • Comparative analysis of humoral immune responses to HIV type 1 envelope glycoproteins in mice immunized with a DNA vaccine, recombinant Semliki Forest virus RNA, or recombinant Semliki Forest virus particles
    • Brand D, Lemiale F, Turbica I, Buzelay L, Brunet S, Barin F: Comparative analysis of humoral immune responses to HIV type 1 envelope glycoproteins in mice immunized with a DNA vaccine, recombinant Semliki Forest virus RNA, or recombinant Semliki Forest virus particles. AIDS Res Hum Retrovir (1998) 14:1369-1377.
    • (1998) AIDS Res Hum Retrovir , vol.14 , pp. 1369-1377
    • Brand, D.1    Lemiale, F.2    Turbica, I.3    Buzelay, L.4    Brunet, S.5    Barin, F.6
  • 36
    • 0029655275 scopus 로고    scopus 로고
    • Sindbis virus DNA-based expression vectors: Utility for in vitro and in vivo gene transfer
    • Dubensky Jr TW, Driver DA, Polo JM, Belli BA, Latham EM, Ibanez CE, Chada S, Brumm D, Banks TA, Mento SJ, Jolly DJ, Chang SM: Sindbis virus DNA-based expression vectors: utility for in vitro and in vivo gene transfer. J Virol (1996) 70:508-519. This paper describes the construction of several Sindbis virus DNA expression vectors and their characterization in vitro and in vivo. Vectors in which the Sindbis replicon sequence was placed downstream of the CMV IE promoter showed higher expression levels than those in which the MoMLV LTR promoter was used. Expression of foreign antigen (β-galactosidase) was shown in muscle cells of mice immunized with the recombinant Sindbis plasmids. Also specific antibodies could be detected against hepatitis B virus (HBV) antigens when mice were immunized with Sindbis plasmids expressing HB V genes c and e.
    • (1996) J Virol , vol.70 , pp. 508-519
    • Dubensky Jr., T.W.1    Driver, D.A.2    Polo, J.M.3    Belli, B.A.4    Latham, E.M.5    Ibanez, C.E.6    Chada, S.7    Brumm, D.8    Banks, T.A.9    Mento, S.J.10    Jolly, D.J.11    Chang, S.M.12
  • 37
    • 0025882069 scopus 로고
    • A pseudoknot-like structure required for efficient self-cleavage of hepatitis delta virus RNA
    • Perrotta AT, Been MD: A pseudoknot-like structure required for efficient self-cleavage of hepatitis delta virus RNA. Nature (1991) 350:434-436.
    • (1991) Nature , vol.350 , pp. 434-436
    • Perrotta, A.T.1    Been, M.D.2
  • 38
    • 0031838647 scopus 로고    scopus 로고
    • Enhancing immune responses using suicidal DNA vaccines
    • Berglund P, Smerdou C, Fleeton MN, Tubulekas I, Liljeström P: Enhancing immune responses using suicidal DNA vaccines. Nat Biotechnol (1998) 16:562-565. A SFV DNA/RNA layered expression system was constructed by placing the SFV replicon sequence in a plasmid downstream of the CMV IE promoter. The vector was improved by fusing the SFV capsid translation enhancer to the amino terminal end of the foreign gene. The expression level of foreign proteins from these vectors in transfected cells were studied and compared with those of conventional DNA plasmids. The transient nature of the SFV DNA vector was shown by the induction of cytopathic effect in the transfected cells. Immunization of mice with these vectors showed a great superiority of the SFV plasmids versus the conventional DNA expression systems, since up to 1000-times more of the latter was necessary to induce similar immune responses.
    • (1998) Nat Biotechnol , vol.16 , pp. 562-565
    • Berglund, P.1    Smerdou, C.2    Fleeton, M.N.3    Tubulekas, I.4    Liljeström, P.5
  • 39
    • 0032540924 scopus 로고    scopus 로고
    • Rapid, high level protein production using DNA-based Semliki Forest virus vectors
    • DiCiommo DP, Bremner R: Rapid, high level protein production using DNA-based Semliki Forest virus vectors. J Biol Chem (1998) 273:18060-18066. A SFV DNA expression plasmid was constructed by placing the SFV replicon sequence downstream of the CMV IE promoter. The expression levels of foreign protein from this vector were found to be higher than those obtained with a similar Sindbis DNA-based vector. The SFV DNA vector was also used to generate recombinant particles by cotransfecting cells with a CMV IE promoter-driven SFV helper plasmid.
    • (1998) J Biol Chem , vol.273 , pp. 18060-18066
    • DiCiommo, D.P.1    Bremner, R.2
  • 40
    • 0031885738 scopus 로고    scopus 로고
    • Semliki Forest virus-based DNA expression vector - Transient protein production followed by cell death
    • Kohno A, Emi N, Kasai M, Tanimoto M, Saito H: Semliki Forest virus-based DNA expression vector - transient protein production followed by cell death. Gene Ther (1998) 5:415-418. This paper describes the construction and characterization of a SFV DNA expression system in which the SFV replicon sequence is placed downstream of the CMV IE promoter. The transient nature of this vector is indirectly shown by using as an indicator of cell death the release of β-galactosidase to the medium in cells transfected with a vector expressing this protein.
    • (1998) Gene Ther , vol.5 , pp. 415-418
    • Kohno, A.1    Emi, N.2    Kasai, M.3    Tanimoto, M.4    Saito, H.5
  • 42
    • 0026922764 scopus 로고
    • Long-term persistence of plasmid DNA and foreign gene expression in mouse muscle
    • Wolff JA, Ludtke JJ, Acsadi G, Williams P, Jani A: Long-term persistence of plasmid DNA and foreign gene expression in mouse muscle. Hum Mol Genet (1992) 1:363-369.
    • (1992) Hum Mol Genet , vol.1 , pp. 363-369
    • Wolff, J.A.1    Ludtke, J.J.2    Acsadi, G.3    Williams, P.4    Jani, A.5
  • 44
    • 0031882102 scopus 로고    scopus 로고
    • DNA immunization against herpes simplex virus: Enhanced efficacy using a Sindbis virus-based vector
    • Hariharan MJ, Driver DA, Townsend K, Brumm D, Polo JM, Belli BA, Catton DJ, Hsu D, Mittelstaedt D, McCormack JE, Karavodin L, Dubensky Jr TW, Chang SM, Banks TA: DNA immunization against herpes simplex virus: enhanced efficacy using a Sindbis virus-based vector. J Virol (1998) 72:950-958. This paper describes the immune responses induced by recombinant Sindbis virus DNA expression vectors expressing the glycoprotein B of herpes simplex virus in mice. Recombinant Sindbis vectors were compared to conventional DNA plasmids expressing the same antigen, and were found to be 100-to 1000-fold more efficient in inducing immune responses in the vaccinated animals. The Sindbis vectors were also able to induce high level of protection from lethal virus challenge in two different murine models at much lower doses than a conventional plasmid.
    • (1998) J Virol , vol.72 , pp. 950-958
    • Hariharan, M.J.1    Driver, D.A.2    Townsend, K.3    Brumm, D.4    Polo, J.M.5    Belli, B.A.6    Catton, D.J.7    Hsu, D.8    Mittelstaedt, D.9    McCormack, J.E.10    Karavodin, L.11    Dubensky Jr., T.W.12    Chang, S.M.13    Banks, T.A.14
  • 45
    • 0028962824 scopus 로고
    • Generation of cytotoxic and humoral immune responses by nonreplicative recombinant Semliki Forest virus
    • Zhou X, Berglund P, Zhao H, Liljeström P, Jondal M: Generation of cytotoxic and humoral immune responses by nonreplicative recombinant Semliki Forest virus. Proc Natl Acad Sci USA (1995) 92:3009-3013.
    • (1995) Proc Natl Acad Sci USA , vol.92 , pp. 3009-3013
    • Zhou, X.1    Berglund, P.2    Zhao, H.3    Liljeström, P.4    Jondal, M.5
  • 46
    • 0031592755 scopus 로고    scopus 로고
    • Comparison of various expression plasmids for the induction of immune response by DNA immunization
    • Lee AH, Suh YS, Sung JH, Yang SH, Sung YC: Comparison of various expression plasmids for the induction of immune response by DNA immunization. Mol Cells (1997) 7:495-501.
    • (1997) Mol Cells , vol.7 , pp. 495-501
    • Lee, A.H.1    Suh, Y.S.2    Sung, J.H.3    Yang, S.H.4    Sung, Y.C.5
  • 47
    • 0000188185 scopus 로고    scopus 로고
    • Interferons and other cytokines
    • Fields BN, Knipe DM, Howley PM (Eds). Lippincott-Raven, Philadelphia
    • Vilcek J, Sen GC: Interferons and other cytokines. In: Fields Virology, Fields BN, Knipe DM, Howley PM (Eds). Lippincott-Raven, Philadelphia (1996):375-399.
    • (1996) Fields Virology , pp. 375-399
    • Vilcek, J.1    Sen, G.C.2
  • 48
    • 0028284024 scopus 로고
    • Expression of IFN A genes in subpopulations of peripheral blood cells
    • Brandt ER, Linnane AW, Devenish RJ: Expression of IFN A genes in subpopulations of peripheral blood cells. Br J Haematol (1994) 86:717-725.
    • (1994) Br J Haematol , vol.86 , pp. 717-725
    • Brandt, E.R.1    Linnane, A.W.2    Devenish, R.J.3
  • 49
    • 0021326655 scopus 로고
    • The pathogenicity of the M9 mutant of Semliki Forest virus in immune-compromised mice
    • Gates MC, Sheahan BJ, Atkins GJ: The pathogenicity of the M9 mutant of Semliki Forest virus in immune-compromised mice. J Gen Virol (1984) 65:73-80.
    • (1984) J Gen Virol , vol.65 , pp. 73-80
    • Gates, M.C.1    Sheahan, B.J.2    Atkins, G.J.3
  • 51
    • 0030906714 scopus 로고    scopus 로고
    • Long-term effects of Semliki Forest virus infection in the mouse central nervous system
    • Donnelly SM, Sheahan BJ, Atkins GJ: Long-term effects of Semliki Forest virus infection in the mouse central nervous system. Neuropathol Appt Neurobiol (1997) 23:235-241.
    • (1997) Neuropathol Appt Neurobiol , vol.23 , pp. 235-241
    • Donnelly, S.M.1    Sheahan, B.J.2    Atkins, G.J.3
  • 52
    • 0032573164 scopus 로고    scopus 로고
    • Noncytopathic Sindbis virus RNA vectors for heterologous gene expression
    • Agapov EV, Frolov I, Lindebach BD, Prágal BM, Schlesinger S, Rice CM: Noncytopathic Sindbis virus RNA vectors for heterologous gene expression. Proc Natl Acad Sci USA (1998) 95:12989-12994. This paper describes the generation of expression vectors based on a noncytopathic Sindbis virus that can be used as RNA or DNA. These vectors can express reasonable amounts of foreign protein in the transfected cells during extended periods of time.
    • (1998) Proc Natl Acad Sci USA , vol.95 , pp. 12989-12994
    • Agapov, E.V.1    Frolov, I.2    Lindebach, B.D.3    Prágal, B.M.4    Schlesinger, S.5    Rice, C.M.6
  • 53
    • 0030938850 scopus 로고    scopus 로고
    • Replication of Flock House virus RNAs from primary transcripts made in cells by RNA polymerase II
    • Johnson KL, Ball LA: Replication of Flock House virus RNAs from primary transcripts made in cells by RNA polymerase II. J Virol (1997) 71:3323-3327.
    • (1997) J Virol , vol.71 , pp. 3323-3327
    • Johnson, K.L.1    Ball, L.A.2


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.