KR20020049031A - 생체내 유전자 송달에 의하여 심혈관 질환을 치료하기위한 기술 및 조성물 - Google Patents
생체내 유전자 송달에 의하여 심혈관 질환을 치료하기위한 기술 및 조성물 Download PDFInfo
- Publication number
- KR20020049031A KR20020049031A KR1020027005855A KR20027005855A KR20020049031A KR 20020049031 A KR20020049031 A KR 20020049031A KR 1020027005855 A KR1020027005855 A KR 1020027005855A KR 20027005855 A KR20027005855 A KR 20027005855A KR 20020049031 A KR20020049031 A KR 20020049031A
- Authority
- KR
- South Korea
- Prior art keywords
- vector
- growth factor
- peptide
- protein
- angiogenic
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 226
- 238000001727 in vivo Methods 0.000 title claims abstract description 45
- 208000024172 Cardiovascular disease Diseases 0.000 title claims abstract description 18
- 239000000203 mixture Substances 0.000 title claims description 52
- 238000001476 gene delivery Methods 0.000 title description 60
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 273
- 239000013598 vector Substances 0.000 claims abstract description 262
- 108010074415 Angiogenic Proteins Proteins 0.000 claims abstract description 212
- 102000008076 Angiogenic Proteins Human genes 0.000 claims abstract description 196
- 210000002216 heart Anatomy 0.000 claims abstract description 109
- 230000002107 myocardial effect Effects 0.000 claims abstract description 88
- 230000000302 ischemic effect Effects 0.000 claims abstract description 53
- 210000004204 blood vessel Anatomy 0.000 claims abstract description 28
- 208000018262 Peripheral vascular disease Diseases 0.000 claims abstract description 15
- 210000004027 cell Anatomy 0.000 claims description 153
- 230000017531 blood circulation Effects 0.000 claims description 118
- 108700019146 Transgenes Proteins 0.000 claims description 105
- 241000701161 unidentified adenovirus Species 0.000 claims description 96
- 230000014509 gene expression Effects 0.000 claims description 85
- 210000001519 tissue Anatomy 0.000 claims description 84
- 108090000380 Fibroblast growth factor 5 Proteins 0.000 claims description 78
- 210000004351 coronary vessel Anatomy 0.000 claims description 76
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 claims description 72
- 102000004169 proteins and genes Human genes 0.000 claims description 69
- 102100028073 Fibroblast growth factor 5 Human genes 0.000 claims description 64
- 230000002491 angiogenic effect Effects 0.000 claims description 61
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 61
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 claims description 58
- 210000004165 myocardium Anatomy 0.000 claims description 56
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims description 55
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims description 53
- 241000700605 Viruses Species 0.000 claims description 52
- 238000002347 injection Methods 0.000 claims description 52
- 239000007924 injection Substances 0.000 claims description 52
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 50
- 230000006870 function Effects 0.000 claims description 49
- 230000001965 increasing effect Effects 0.000 claims description 49
- 102000013275 Somatomedins Human genes 0.000 claims description 46
- 102000018233 Fibroblast Growth Factor Human genes 0.000 claims description 40
- 108050007372 Fibroblast Growth Factor Proteins 0.000 claims description 40
- 229940126864 fibroblast growth factor Drugs 0.000 claims description 40
- 108090000381 Fibroblast growth factor 4 Proteins 0.000 claims description 39
- 102100028072 Fibroblast growth factor 4 Human genes 0.000 claims description 36
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical group NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 claims description 33
- 108010076504 Protein Sorting Signals Proteins 0.000 claims description 33
- 239000002245 particle Substances 0.000 claims description 32
- 239000013603 viral vector Substances 0.000 claims description 32
- 230000010412 perfusion Effects 0.000 claims description 30
- 210000001367 artery Anatomy 0.000 claims description 29
- 238000001415 gene therapy Methods 0.000 claims description 29
- 208000031225 myocardial ischemia Diseases 0.000 claims description 29
- 229920001184 polypeptide Polymers 0.000 claims description 27
- 230000010076 replication Effects 0.000 claims description 27
- 239000002550 vasoactive agent Substances 0.000 claims description 25
- 210000004369 blood Anatomy 0.000 claims description 24
- 239000008280 blood Substances 0.000 claims description 24
- 230000008602 contraction Effects 0.000 claims description 22
- 230000002950 deficient Effects 0.000 claims description 20
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 claims description 18
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 claims description 18
- 208000028867 ischemia Diseases 0.000 claims description 18
- 210000002027 skeletal muscle Anatomy 0.000 claims description 17
- 229960001340 histamine Drugs 0.000 claims description 16
- 210000004413 cardiac myocyte Anatomy 0.000 claims description 14
- 238000001802 infusion Methods 0.000 claims description 12
- 108090000386 Fibroblast Growth Factor 1 Proteins 0.000 claims description 11
- 102100031706 Fibroblast growth factor 1 Human genes 0.000 claims description 11
- 230000001939 inductive effect Effects 0.000 claims description 11
- 230000009261 transgenic effect Effects 0.000 claims description 11
- 210000003462 vein Anatomy 0.000 claims description 11
- 230000008828 contractile function Effects 0.000 claims description 10
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 claims description 9
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 claims description 9
- 210000000663 muscle cell Anatomy 0.000 claims description 9
- 239000000243 solution Substances 0.000 claims description 9
- 239000003453 histamine agonist Substances 0.000 claims description 8
- 206010021143 Hypoxia Diseases 0.000 claims description 7
- 102000005604 Myosin Heavy Chains Human genes 0.000 claims description 7
- 108010084498 Myosin Heavy Chains Proteins 0.000 claims description 7
- 102000016349 Myosin Light Chains Human genes 0.000 claims description 7
- 108010067385 Myosin Light Chains Proteins 0.000 claims description 7
- 238000011161 development Methods 0.000 claims description 7
- 230000003362 replicative effect Effects 0.000 claims description 7
- 201000001320 Atherosclerosis Diseases 0.000 claims description 6
- 108090000382 Fibroblast growth factor 6 Proteins 0.000 claims description 6
- 230000001737 promoting effect Effects 0.000 claims description 6
- 102100028075 Fibroblast growth factor 6 Human genes 0.000 claims description 5
- 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 claims description 5
- 210000001105 femoral artery Anatomy 0.000 claims description 5
- 230000012010 growth Effects 0.000 claims description 5
- 210000002064 heart cell Anatomy 0.000 claims description 5
- 206010020718 hyperplasia Diseases 0.000 claims description 5
- 102100037852 Insulin-like growth factor I Human genes 0.000 claims description 4
- 108010073923 Vascular Endothelial Growth Factor C Proteins 0.000 claims description 4
- 102000009520 Vascular Endothelial Growth Factor C Human genes 0.000 claims description 4
- 210000002950 fibroblast Anatomy 0.000 claims description 4
- 241000283690 Bos taurus Species 0.000 claims description 3
- 230000001919 adrenal effect Effects 0.000 claims description 2
- 239000003102 growth factor Substances 0.000 claims description 2
- 210000001349 mammary artery Anatomy 0.000 claims description 2
- 230000007954 hypoxia Effects 0.000 claims 5
- 108010073925 Vascular Endothelial Growth Factor B Proteins 0.000 claims 3
- 102100039037 Vascular endothelial growth factor A Human genes 0.000 claims 3
- 102100038217 Vascular endothelial growth factor B Human genes 0.000 claims 3
- 239000004037 angiogenesis inhibitor Substances 0.000 claims 2
- 210000003556 vascular endothelial cell Anatomy 0.000 claims 2
- 210000004004 carotid artery internal Anatomy 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 229940124531 pharmaceutical excipient Drugs 0.000 claims 1
- 208000019622 heart disease Diseases 0.000 abstract description 32
- 230000002093 peripheral effect Effects 0.000 abstract description 14
- 241001465754 Metazoa Species 0.000 description 110
- 238000012546 transfer Methods 0.000 description 109
- 206010019280 Heart failures Diseases 0.000 description 55
- 230000002861 ventricular Effects 0.000 description 43
- 230000033115 angiogenesis Effects 0.000 description 39
- 206010007559 Cardiac failure congestive Diseases 0.000 description 37
- 230000000694 effects Effects 0.000 description 36
- 238000011282 treatment Methods 0.000 description 34
- 230000004087 circulation Effects 0.000 description 33
- 239000013612 plasmid Substances 0.000 description 33
- 230000000747 cardiac effect Effects 0.000 description 32
- 101150066555 lacZ gene Proteins 0.000 description 30
- 230000003612 virological effect Effects 0.000 description 29
- 101150021185 FGF gene Proteins 0.000 description 26
- 230000001976 improved effect Effects 0.000 description 25
- 210000001736 capillary Anatomy 0.000 description 24
- 230000002792 vascular Effects 0.000 description 24
- 208000024891 symptom Diseases 0.000 description 23
- 238000003752 polymerase chain reaction Methods 0.000 description 22
- 208000010125 myocardial infarction Diseases 0.000 description 21
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 20
- 238000005259 measurement Methods 0.000 description 20
- 108091033319 polynucleotide Proteins 0.000 description 20
- 102000040430 polynucleotide Human genes 0.000 description 20
- 239000002157 polynucleotide Substances 0.000 description 20
- 108091026890 Coding region Proteins 0.000 description 19
- 108020004414 DNA Proteins 0.000 description 19
- 230000035882 stress Effects 0.000 description 18
- 208000029078 coronary artery disease Diseases 0.000 description 17
- 230000004064 dysfunction Effects 0.000 description 17
- 230000008719 thickening Effects 0.000 description 17
- 108010048367 enhanced green fluorescent protein Proteins 0.000 description 16
- 230000001225 therapeutic effect Effects 0.000 description 16
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 15
- 239000000835 fiber Substances 0.000 description 15
- 241000282887 Suidae Species 0.000 description 14
- 238000004458 analytical method Methods 0.000 description 14
- 230000001746 atrial effect Effects 0.000 description 14
- 238000002592 echocardiography Methods 0.000 description 14
- 206010020880 Hypertrophy Diseases 0.000 description 13
- 241000282898 Sus scrofa Species 0.000 description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 13
- 239000012634 fragment Substances 0.000 description 13
- 210000004185 liver Anatomy 0.000 description 13
- 239000013607 AAV vector Substances 0.000 description 12
- 208000033774 Ventricular Remodeling Diseases 0.000 description 12
- 201000010099 disease Diseases 0.000 description 12
- 230000003248 secreting effect Effects 0.000 description 12
- 230000028327 secretion Effects 0.000 description 12
- 238000000540 analysis of variance Methods 0.000 description 11
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 11
- 230000007423 decrease Effects 0.000 description 11
- 239000003550 marker Substances 0.000 description 11
- 239000001301 oxygen Substances 0.000 description 11
- 229910052760 oxygen Inorganic materials 0.000 description 11
- 206010002383 Angina Pectoris Diseases 0.000 description 10
- 241001135569 Human adenovirus 5 Species 0.000 description 10
- 206010061216 Infarction Diseases 0.000 description 10
- 239000003795 chemical substances by application Substances 0.000 description 10
- 230000007574 infarction Effects 0.000 description 10
- 238000004519 manufacturing process Methods 0.000 description 10
- 230000001404 mediated effect Effects 0.000 description 10
- 239000011780 sodium chloride Substances 0.000 description 10
- 206010061218 Inflammation Diseases 0.000 description 9
- 108010005774 beta-Galactosidase Proteins 0.000 description 9
- 102000005936 beta-Galactosidase Human genes 0.000 description 9
- 230000004217 heart function Effects 0.000 description 9
- 230000000004 hemodynamic effect Effects 0.000 description 9
- 230000004054 inflammatory process Effects 0.000 description 9
- 150000002632 lipids Chemical class 0.000 description 9
- 239000002609 medium Substances 0.000 description 9
- 238000013310 pig model Methods 0.000 description 9
- 230000002829 reductive effect Effects 0.000 description 9
- 230000008685 targeting Effects 0.000 description 9
- 238000013518 transcription Methods 0.000 description 9
- 230000035897 transcription Effects 0.000 description 9
- 210000005166 vasculature Anatomy 0.000 description 9
- 210000000596 ventricular septum Anatomy 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 101150075174 E1B gene Proteins 0.000 description 8
- 238000010171 animal model Methods 0.000 description 8
- 238000013459 approach Methods 0.000 description 8
- 230000008859 change Effects 0.000 description 8
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 8
- 239000003623 enhancer Substances 0.000 description 8
- 230000006872 improvement Effects 0.000 description 8
- 208000015181 infectious disease Diseases 0.000 description 8
- 210000005240 left ventricle Anatomy 0.000 description 8
- 108020004999 messenger RNA Proteins 0.000 description 8
- 210000003205 muscle Anatomy 0.000 description 8
- 239000002953 phosphate buffered saline Substances 0.000 description 8
- 210000001147 pulmonary artery Anatomy 0.000 description 8
- 230000009467 reduction Effects 0.000 description 8
- 239000013605 shuttle vector Substances 0.000 description 8
- 208000031229 Cardiomyopathies Diseases 0.000 description 7
- 108020005202 Viral DNA Proteins 0.000 description 7
- 230000008901 benefit Effects 0.000 description 7
- 230000027455 binding Effects 0.000 description 7
- AIYUHDOJVYHVIT-UHFFFAOYSA-M caesium chloride Chemical compound [Cl-].[Cs+] AIYUHDOJVYHVIT-UHFFFAOYSA-M 0.000 description 7
- 230000002708 enhancing effect Effects 0.000 description 7
- 210000005259 peripheral blood Anatomy 0.000 description 7
- 239000011886 peripheral blood Substances 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- 210000002966 serum Anatomy 0.000 description 7
- 238000001356 surgical procedure Methods 0.000 description 7
- 238000005199 ultracentrifugation Methods 0.000 description 7
- 241000282412 Homo Species 0.000 description 6
- 206010030113 Oedema Diseases 0.000 description 6
- 238000010162 Tukey test Methods 0.000 description 6
- 108010067390 Viral Proteins Proteins 0.000 description 6
- 210000000709 aorta Anatomy 0.000 description 6
- 230000009286 beneficial effect Effects 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 230000000157 blood function Effects 0.000 description 6
- 230000037396 body weight Effects 0.000 description 6
- 238000004113 cell culture Methods 0.000 description 6
- 238000010367 cloning Methods 0.000 description 6
- 239000002299 complementary DNA Substances 0.000 description 6
- 230000018109 developmental process Effects 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 230000001771 impaired effect Effects 0.000 description 6
- 210000005246 left atrium Anatomy 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 230000017074 necrotic cell death Effects 0.000 description 6
- 230000008488 polyadenylation Effects 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 210000001525 retina Anatomy 0.000 description 6
- 238000010186 staining Methods 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 238000001890 transfection Methods 0.000 description 6
- OPIFSICVWOWJMJ-AEOCFKNESA-N 5-bromo-4-chloro-3-indolyl beta-D-galactoside Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1OC1=CNC2=CC=C(Br)C(Cl)=C12 OPIFSICVWOWJMJ-AEOCFKNESA-N 0.000 description 5
- 206010013975 Dyspnoeas Diseases 0.000 description 5
- 206010028851 Necrosis Diseases 0.000 description 5
- 208000030831 Peripheral arterial occlusive disease Diseases 0.000 description 5
- 230000001154 acute effect Effects 0.000 description 5
- 150000001413 amino acids Chemical class 0.000 description 5
- 239000002870 angiogenesis inducing agent Substances 0.000 description 5
- 230000000875 corresponding effect Effects 0.000 description 5
- XEYBHCRIKKKOSS-UHFFFAOYSA-N disodium;azanylidyneoxidanium;iron(2+);pentacyanide Chemical compound [Na+].[Na+].[Fe+2].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].[O+]#N XEYBHCRIKKKOSS-UHFFFAOYSA-N 0.000 description 5
- 230000002169 extracardiac Effects 0.000 description 5
- 239000012530 fluid Substances 0.000 description 5
- 230000037406 food intake Effects 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 238000010253 intravenous injection Methods 0.000 description 5
- 230000008338 local blood flow Effects 0.000 description 5
- 210000004962 mammalian cell Anatomy 0.000 description 5
- 238000007431 microscopic evaluation Methods 0.000 description 5
- 230000035755 proliferation Effects 0.000 description 5
- 230000000644 propagated effect Effects 0.000 description 5
- 230000002685 pulmonary effect Effects 0.000 description 5
- 238000011160 research Methods 0.000 description 5
- 229940083618 sodium nitroprusside Drugs 0.000 description 5
- 230000000638 stimulation Effects 0.000 description 5
- 230000009885 systemic effect Effects 0.000 description 5
- 229910052716 thallium Inorganic materials 0.000 description 5
- BKVIYDNLLOSFOA-UHFFFAOYSA-N thallium Chemical compound [Tl] BKVIYDNLLOSFOA-UHFFFAOYSA-N 0.000 description 5
- 241000282472 Canis lupus familiaris Species 0.000 description 4
- 208000000059 Dyspnea Diseases 0.000 description 4
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 4
- 101000808011 Homo sapiens Vascular endothelial growth factor A Proteins 0.000 description 4
- 208000009525 Myocarditis Diseases 0.000 description 4
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical group O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 208000009982 Ventricular Dysfunction Diseases 0.000 description 4
- 238000009825 accumulation Methods 0.000 description 4
- 125000003275 alpha amino acid group Chemical group 0.000 description 4
- 230000000692 anti-sense effect Effects 0.000 description 4
- 230000036770 blood supply Effects 0.000 description 4
- 239000007853 buffer solution Substances 0.000 description 4
- 210000001715 carotid artery Anatomy 0.000 description 4
- 108091092356 cellular DNA Proteins 0.000 description 4
- 210000003793 centrosome Anatomy 0.000 description 4
- 210000000038 chest Anatomy 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 4
- 230000000120 cytopathologic effect Effects 0.000 description 4
- 230000034994 death Effects 0.000 description 4
- 231100000517 death Toxicity 0.000 description 4
- 238000012217 deletion Methods 0.000 description 4
- 230000037430 deletion Effects 0.000 description 4
- 210000001174 endocardium Anatomy 0.000 description 4
- 210000002889 endothelial cell Anatomy 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 102000058223 human VEGFA Human genes 0.000 description 4
- 238000003384 imaging method Methods 0.000 description 4
- 230000000977 initiatory effect Effects 0.000 description 4
- 239000002502 liposome Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 230000007774 longterm Effects 0.000 description 4
- 230000002503 metabolic effect Effects 0.000 description 4
- 210000000107 myocyte Anatomy 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 235000015097 nutrients Nutrition 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- 239000013641 positive control Substances 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 230000006798 recombination Effects 0.000 description 4
- 238000005215 recombination Methods 0.000 description 4
- 210000005241 right ventricle Anatomy 0.000 description 4
- 238000010561 standard procedure Methods 0.000 description 4
- 230000006815 ventricular dysfunction Effects 0.000 description 4
- 238000001262 western blot Methods 0.000 description 4
- 206010003210 Arteriosclerosis Diseases 0.000 description 3
- 208000020446 Cardiac disease Diseases 0.000 description 3
- 206010007558 Cardiac failure chronic Diseases 0.000 description 3
- 208000006029 Cardiomegaly Diseases 0.000 description 3
- 230000006820 DNA synthesis Effects 0.000 description 3
- 102000016911 Deoxyribonucleases Human genes 0.000 description 3
- 108010053770 Deoxyribonucleases Proteins 0.000 description 3
- 241000702421 Dependoparvovirus Species 0.000 description 3
- 206010013012 Dilatation ventricular Diseases 0.000 description 3
- 201000010046 Dilated cardiomyopathy Diseases 0.000 description 3
- 206010016654 Fibrosis Diseases 0.000 description 3
- 101100446512 Homo sapiens FGF4 gene Proteins 0.000 description 3
- 241000725303 Human immunodeficiency virus Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 229920005654 Sephadex Polymers 0.000 description 3
- 239000012507 Sephadex™ Substances 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 230000006978 adaptation Effects 0.000 description 3
- 238000002399 angioplasty Methods 0.000 description 3
- 210000004102 animal cell Anatomy 0.000 description 3
- 230000004872 arterial blood pressure Effects 0.000 description 3
- 208000011775 arteriosclerosis disease Diseases 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 230000003915 cell function Effects 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 210000000349 chromosome Anatomy 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 230000007812 deficiency Effects 0.000 description 3
- 238000002716 delivery method Methods 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 230000009977 dual effect Effects 0.000 description 3
- 230000002526 effect on cardiovascular system Effects 0.000 description 3
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 3
- 230000001747 exhibiting effect Effects 0.000 description 3
- 210000001508 eye Anatomy 0.000 description 3
- 230000004761 fibrosis Effects 0.000 description 3
- 229930182830 galactose Natural products 0.000 description 3
- 210000005003 heart tissue Anatomy 0.000 description 3
- 230000028993 immune response Effects 0.000 description 3
- 238000003119 immunoblot Methods 0.000 description 3
- 230000008595 infiltration Effects 0.000 description 3
- 238000001764 infiltration Methods 0.000 description 3
- 210000004969 inflammatory cell Anatomy 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 238000011835 investigation Methods 0.000 description 3
- 208000010729 leg swelling Diseases 0.000 description 3
- 230000003211 malignant effect Effects 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 230000010016 myocardial function Effects 0.000 description 3
- 239000013642 negative control Substances 0.000 description 3
- 239000002840 nitric oxide donor Substances 0.000 description 3
- 102000039446 nucleic acids Human genes 0.000 description 3
- 108020004707 nucleic acids Proteins 0.000 description 3
- 150000007523 nucleic acids Chemical class 0.000 description 3
- 239000002773 nucleotide Substances 0.000 description 3
- 125000003729 nucleotide group Chemical class 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 230000000750 progressive effect Effects 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 238000007634 remodeling Methods 0.000 description 3
- 230000001177 retroviral effect Effects 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 238000005070 sampling Methods 0.000 description 3
- 230000035945 sensitivity Effects 0.000 description 3
- 239000012679 serum free medium Substances 0.000 description 3
- 238000004904 shortening Methods 0.000 description 3
- 238000010361 transduction Methods 0.000 description 3
- 230000026683 transduction Effects 0.000 description 3
- 241001430294 unidentified retrovirus Species 0.000 description 3
- 238000011144 upstream manufacturing Methods 0.000 description 3
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 2
- YQNRVGJCPCNMKT-LFVJCYFKSA-N 2-[(e)-[[2-(4-benzylpiperazin-1-ium-1-yl)acetyl]hydrazinylidene]methyl]-6-prop-2-enylphenolate Chemical compound [O-]C1=C(CC=C)C=CC=C1\C=N\NC(=O)C[NH+]1CCN(CC=2C=CC=CC=2)CC1 YQNRVGJCPCNMKT-LFVJCYFKSA-N 0.000 description 2
- 239000005541 ACE inhibitor Substances 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 2
- 102100030988 Angiotensin-converting enzyme Human genes 0.000 description 2
- 206010003445 Ascites Diseases 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 101100462537 Caenorhabditis elegans pac-1 gene Proteins 0.000 description 2
- 101100421423 Caenorhabditis elegans spl-1 gene Proteins 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- 206010056370 Congestive cardiomyopathy Diseases 0.000 description 2
- 201000000057 Coronary Stenosis Diseases 0.000 description 2
- 241000557626 Corvus corax Species 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- 102100031780 Endonuclease Human genes 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 2
- 102000003745 Hepatocyte Growth Factor Human genes 0.000 description 2
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 description 2
- 102000000589 Interleukin-1 Human genes 0.000 description 2
- 108010002352 Interleukin-1 Proteins 0.000 description 2
- 238000000134 MTT assay Methods 0.000 description 2
- 231100000002 MTT assay Toxicity 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 101100117764 Mus musculus Dusp2 gene Proteins 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 102000011779 Nitric Oxide Synthase Type II Human genes 0.000 description 2
- 108010076864 Nitric Oxide Synthase Type II Proteins 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 108700008625 Reporter Genes Proteins 0.000 description 2
- 229920002684 Sepharose Polymers 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 206010053648 Vascular occlusion Diseases 0.000 description 2
- 206010047281 Ventricular arrhythmia Diseases 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000009102 absorption Effects 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- GFFGJBXGBJISGV-UHFFFAOYSA-N adenyl group Chemical class N1=CN=C2N=CNC2=C1N GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 2
- 230000001800 adrenalinergic effect Effects 0.000 description 2
- 239000000674 adrenergic antagonist Substances 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 2
- 230000003143 atherosclerotic effect Effects 0.000 description 2
- 238000011888 autopsy Methods 0.000 description 2
- -1 betahistamine Chemical compound 0.000 description 2
- 238000001574 biopsy Methods 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 230000008822 capillary blood flow Effects 0.000 description 2
- 230000009084 cardiovascular function Effects 0.000 description 2
- 230000032823 cell division Effects 0.000 description 2
- 238000001516 cell proliferation assay Methods 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 230000002759 chromosomal effect Effects 0.000 description 2
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 2
- 230000003750 conditioning effect Effects 0.000 description 2
- 239000000356 contaminant Substances 0.000 description 2
- 230000002596 correlated effect Effects 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 230000001627 detrimental effect Effects 0.000 description 2
- 238000000502 dialysis Methods 0.000 description 2
- 230000010339 dilation Effects 0.000 description 2
- 239000002934 diuretic Substances 0.000 description 2
- 229940030606 diuretics Drugs 0.000 description 2
- 238000002651 drug therapy Methods 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 238000002523 gelfiltration Methods 0.000 description 2
- 210000002837 heart atrium Anatomy 0.000 description 2
- 208000014951 hematologic disease Diseases 0.000 description 2
- 229960002897 heparin Drugs 0.000 description 2
- 229920000669 heparin Polymers 0.000 description 2
- 230000028709 inflammatory response Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 230000010354 integration Effects 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 238000010255 intramuscular injection Methods 0.000 description 2
- 239000007927 intramuscular injection Substances 0.000 description 2
- 238000007913 intrathecal administration Methods 0.000 description 2
- 230000002427 irreversible effect Effects 0.000 description 2
- 238000001638 lipofection Methods 0.000 description 2
- 230000004807 localization Effects 0.000 description 2
- 230000033001 locomotion Effects 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 230000002438 mitochondrial effect Effects 0.000 description 2
- 239000003226 mitogen Substances 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 229960002748 norepinephrine Drugs 0.000 description 2
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 2
- 235000021048 nutrient requirements Nutrition 0.000 description 2
- 230000003204 osmotic effect Effects 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- XQYZDYMELSJDRZ-UHFFFAOYSA-N papaverine Chemical compound C1=C(OC)C(OC)=CC=C1CC1=NC=CC2=CC(OC)=C(OC)C=C12 XQYZDYMELSJDRZ-UHFFFAOYSA-N 0.000 description 2
- 230000000737 periodic effect Effects 0.000 description 2
- 230000002085 persistent effect Effects 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 238000011458 pharmacological treatment Methods 0.000 description 2
- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 2
- 229960001802 phenylephrine Drugs 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 238000010837 poor prognosis Methods 0.000 description 2
- 238000010149 post-hoc-test Methods 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 238000004393 prognosis Methods 0.000 description 2
- 239000013608 rAAV vector Substances 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 230000000284 resting effect Effects 0.000 description 2
- 230000000250 revascularization Effects 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 210000000115 thoracic cavity Anatomy 0.000 description 2
- 229940104230 thymidine Drugs 0.000 description 2
- 230000002103 transcriptional effect Effects 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- 230000014616 translation Effects 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- 230000006459 vascular development Effects 0.000 description 2
- 208000021331 vascular occlusion disease Diseases 0.000 description 2
- 206010047302 ventricular tachycardia Diseases 0.000 description 2
- 230000029812 viral genome replication Effects 0.000 description 2
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 1
- XDKYTXBAVJELDQ-UHFFFAOYSA-N 2-methylhistamine Chemical compound CC1=NC=C(CCN)N1 XDKYTXBAVJELDQ-UHFFFAOYSA-N 0.000 description 1
- XPQIPUZPSLAZDV-UHFFFAOYSA-N 2-pyridylethylamine Chemical compound NCCC1=CC=CC=N1 XPQIPUZPSLAZDV-UHFFFAOYSA-N 0.000 description 1
- 229930008281 A03AD01 - Papaverine Natural products 0.000 description 1
- 206010001258 Adenoviral infections Diseases 0.000 description 1
- 241000701242 Adenoviridae Species 0.000 description 1
- 108010024878 Adenovirus E1A Proteins Proteins 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 101710129690 Angiotensin-converting enzyme inhibitor Proteins 0.000 description 1
- 208000002267 Anti-neutrophil cytoplasmic antibody-associated vasculitis Diseases 0.000 description 1
- 101100215647 Aspergillus flavus (strain ATCC 200026 / FGSC A1120 / IAM 13836 / NRRL 3357 / JCM 12722 / SRRC 167) aflR gene Proteins 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 206010003591 Ataxia Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 208000019838 Blood disease Diseases 0.000 description 1
- 101710086378 Bradykinin-potentiating and C-type natriuretic peptides Proteins 0.000 description 1
- 101100450705 Caenorhabditis elegans hif-1 gene Proteins 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- 206010007556 Cardiac failure acute Diseases 0.000 description 1
- 206010048610 Cardiotoxicity Diseases 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 206010008479 Chest Pain Diseases 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- 206010069729 Collateral circulation Diseases 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 208000001778 Coronary Occlusion Diseases 0.000 description 1
- 201000000054 Coronary Restenosis Diseases 0.000 description 1
- 206010011086 Coronary artery occlusion Diseases 0.000 description 1
- 206010056489 Coronary artery restenosis Diseases 0.000 description 1
- 206010011089 Coronary artery stenosis Diseases 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 102000012410 DNA Ligases Human genes 0.000 description 1
- 108010061982 DNA Ligases Proteins 0.000 description 1
- 102000052510 DNA-Binding Proteins Human genes 0.000 description 1
- 108700020911 DNA-Binding Proteins Proteins 0.000 description 1
- 240000001879 Digitalis lutea Species 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 206010014418 Electrolyte imbalance Diseases 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 238000012276 Endovascular treatment Methods 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 108700039887 Essential Genes Proteins 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- 241000713800 Feline immunodeficiency virus Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 101800000194 Growth hormone-binding protein Proteins 0.000 description 1
- 102400001066 Growth hormone-binding protein Human genes 0.000 description 1
- 208000010496 Heart Arrest Diseases 0.000 description 1
- 101100281008 Homo sapiens FGF2 gene Proteins 0.000 description 1
- 101001060267 Homo sapiens Fibroblast growth factor 5 Proteins 0.000 description 1
- 101000687346 Homo sapiens PR domain zinc finger protein 2 Proteins 0.000 description 1
- 241000701131 Human adenovirus 14 Species 0.000 description 1
- 241000598171 Human adenovirus sp. Species 0.000 description 1
- 241000701024 Human betaherpesvirus 5 Species 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010058558 Hypoperfusion Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102000003777 Interleukin-1 beta Human genes 0.000 description 1
- 108090000193 Interleukin-1 beta Proteins 0.000 description 1
- 208000007766 Kaposi sarcoma Diseases 0.000 description 1
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
- 206010049694 Left Ventricular Dysfunction Diseases 0.000 description 1
- 241000713666 Lentivirus Species 0.000 description 1
- 108090000362 Lymphotoxin-beta Proteins 0.000 description 1
- 101001055320 Myxine glutinosa Insulin-like growth factor Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 102100028452 Nitric oxide synthase, endothelial Human genes 0.000 description 1
- 101710090055 Nitric oxide synthase, endothelial Proteins 0.000 description 1
- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 1
- 239000000006 Nitroglycerin Substances 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 238000002944 PCR assay Methods 0.000 description 1
- 102100024885 PR domain zinc finger protein 2 Human genes 0.000 description 1
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 1
- 208000005764 Peripheral Arterial Disease Diseases 0.000 description 1
- 206010034576 Peripheral ischaemia Diseases 0.000 description 1
- 208000028872 Progressive muscular dystrophy Diseases 0.000 description 1
- 108010059712 Pronase Proteins 0.000 description 1
- 241000125945 Protoparvovirus Species 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 108091005682 Receptor kinases Proteins 0.000 description 1
- 206010038687 Respiratory distress Diseases 0.000 description 1
- 241000220010 Rhode Species 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 108091058545 Secretory proteins Proteins 0.000 description 1
- 102000040739 Secretory proteins Human genes 0.000 description 1
- 206010049418 Sudden Cardiac Death Diseases 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- TWZOYAWHWDRMEZ-UHFFFAOYSA-N Thiazolylethylamine Chemical compound NCCC1=NC=CS1 TWZOYAWHWDRMEZ-UHFFFAOYSA-N 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 102000013534 Troponin C Human genes 0.000 description 1
- 102000009524 Vascular Endothelial Growth Factor A Human genes 0.000 description 1
- 206010047139 Vasoconstriction Diseases 0.000 description 1
- 108700005077 Viral Genes Proteins 0.000 description 1
- 108020000999 Viral RNA Proteins 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- HOBWAPHTEJGALG-JKCMADFCSA-N [(1r,5s)-8-methyl-8-azoniabicyclo[3.2.1]octan-3-yl] 3-hydroxy-2-phenylpropanoate;sulfate Chemical compound [O-]S([O-])(=O)=O.C([C@H]1CC[C@@H](C2)[NH+]1C)C2OC(=O)C(CO)C1=CC=CC=C1.C([C@H]1CC[C@@H](C2)[NH+]1C)C2OC(=O)C(CO)C1=CC=CC=C1 HOBWAPHTEJGALG-JKCMADFCSA-N 0.000 description 1
- OSAIGCUMGMJCMC-HCWSKCQFSA-N [(2s,3r,4s,5r)-2-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy hypobromite Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@@]1(OOBr)N1C(=O)NC(=O)C=C1 OSAIGCUMGMJCMC-HCWSKCQFSA-N 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 230000002730 additional effect Effects 0.000 description 1
- 108700010877 adenoviridae proteins Proteins 0.000 description 1
- 102000030621 adenylate cyclase Human genes 0.000 description 1
- 108060000200 adenylate cyclase Proteins 0.000 description 1
- 239000000048 adrenergic agonist Substances 0.000 description 1
- 229940126157 adrenergic receptor agonist Drugs 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- 230000004520 agglutination Effects 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 229940025084 amphetamine Drugs 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- 238000002266 amputation Methods 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 230000002424 anti-apoptotic effect Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 210000000702 aorta abdominal Anatomy 0.000 description 1
- 210000002565 arteriole Anatomy 0.000 description 1
- 230000001174 ascending effect Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 229960002028 atropine sulfate Drugs 0.000 description 1
- 230000003416 augmentation Effects 0.000 description 1
- 238000010009 beating Methods 0.000 description 1
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 1
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 210000002302 brachial artery Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 239000000480 calcium channel blocker Substances 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 231100000259 cardiotoxicity Toxicity 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 150000003943 catecholamines Chemical class 0.000 description 1
- 230000003822 cell turnover Effects 0.000 description 1
- 210000004718 centriole Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000012761 co-transfection Methods 0.000 description 1
- 210000003477 cochlea Anatomy 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 208000014387 congenital coronary artery anomaly Diseases 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000009989 contractile response Effects 0.000 description 1
- 239000002872 contrast media Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 201000011639 coronary artery anomaly Diseases 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 230000001351 cycling effect Effects 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000000881 depressing effect Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000003205 diastolic effect Effects 0.000 description 1
- VCRMDEZFONERTH-UHFFFAOYSA-L dicesium;dichloride Chemical compound [Cl-].[Cl-].[Cs+].[Cs+] VCRMDEZFONERTH-UHFFFAOYSA-L 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 201000011304 dilated cardiomyopathy 1A Diseases 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000002183 duodenal effect Effects 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 210000002308 embryonic cell Anatomy 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 210000003989 endothelium vascular Anatomy 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 210000003414 extremity Anatomy 0.000 description 1
- 208000012955 familial cardiomyopathy Diseases 0.000 description 1
- 208000004996 familial dilated cardiomyopathy Diseases 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000009760 functional impairment Effects 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 229960003711 glyceryl trinitrate Drugs 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 210000002288 golgi apparatus Anatomy 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- BCQZXOMGPXTTIC-UHFFFAOYSA-N halothane Chemical compound FC(F)(F)C(Cl)Br BCQZXOMGPXTTIC-UHFFFAOYSA-N 0.000 description 1
- 229960003132 halothane Drugs 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000018706 hematopoietic system disease Diseases 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000010562 histological examination Methods 0.000 description 1
- 230000006801 homologous recombination Effects 0.000 description 1
- 238000002744 homologous recombination Methods 0.000 description 1
- 102000057233 human FGF5 Human genes 0.000 description 1
- 102000044162 human IGF1 Human genes 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 208000003532 hypothyroidism Diseases 0.000 description 1
- 230000002989 hypothyroidism Effects 0.000 description 1
- 210000003090 iliac artery Anatomy 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 238000003365 immunocytochemistry Methods 0.000 description 1
- 230000002055 immunohistochemical effect Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 239000003049 inorganic solvent Substances 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 229960003299 ketamine Drugs 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 230000001926 lymphatic effect Effects 0.000 description 1
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 229940100630 metacresol Drugs 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- 230000008747 mitogenic response Effects 0.000 description 1
- 230000000394 mitotic effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 230000004220 muscle function Effects 0.000 description 1
- 201000006938 muscular dystrophy Diseases 0.000 description 1
- 108010067198 mutein 2 Proteins 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- 208000037891 myocardial injury Diseases 0.000 description 1
- 208000002089 myocardial stunning Diseases 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- PGSADBUBUOPOJS-UHFFFAOYSA-N neutral red Chemical compound Cl.C1=C(C)C(N)=CC2=NC3=CC(N(C)C)=CC=C3N=C21 PGSADBUBUOPOJS-UHFFFAOYSA-N 0.000 description 1
- 231100000989 no adverse effect Toxicity 0.000 description 1
- 230000030648 nucleus localization Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000012261 overproduction Methods 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 229960001789 papaverine Drugs 0.000 description 1
- 210000003540 papillary muscle Anatomy 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 230000001314 paroxysmal effect Effects 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 210000003516 pericardium Anatomy 0.000 description 1
- 230000036581 peripheral resistance Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 230000006461 physiological response Effects 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 108010017843 platelet-derived growth factor A Proteins 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 230000026341 positive regulation of angiogenesis Effects 0.000 description 1
- 108091005626 post-translationally modified proteins Proteins 0.000 description 1
- 102000035123 post-translationally modified proteins Human genes 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 230000003334 potential effect Effects 0.000 description 1
- 101150086745 pre gene Proteins 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000036316 preload Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 210000003492 pulmonary vein Anatomy 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 230000009103 reabsorption Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 102000037983 regulatory factors Human genes 0.000 description 1
- 108091008025 regulatory factors Proteins 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 230000001718 repressive effect Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000020874 response to hypoxia Effects 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000009962 secretion pathway Effects 0.000 description 1
- 210000004911 serous fluid Anatomy 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 230000037432 silent mutation Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- HELHAJAZNSDZJO-OLXYHTOASA-L sodium L-tartrate Chemical compound [Na+].[Na+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O HELHAJAZNSDZJO-OLXYHTOASA-L 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000001433 sodium tartrate Substances 0.000 description 1
- 229960002167 sodium tartrate Drugs 0.000 description 1
- 235000011004 sodium tartrates Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 208000014221 sudden cardiac arrest Diseases 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000011477 surgical intervention Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 229920002994 synthetic fiber Polymers 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000007838 tissue remodeling Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000002627 tracheal intubation Methods 0.000 description 1
- 238000012250 transgenic expression Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 238000010967 transthoracic echocardiography Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 208000037995 tubular obstruction Diseases 0.000 description 1
- 238000007492 two-way ANOVA Methods 0.000 description 1
- 230000004218 vascular function Effects 0.000 description 1
- 230000008728 vascular permeability Effects 0.000 description 1
- 238000007631 vascular surgery Methods 0.000 description 1
- 230000025033 vasoconstriction Effects 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 230000002087 whitening effect Effects 0.000 description 1
- 108010088577 zinc-binding protein Proteins 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/475—Growth factors; Growth regulators
- C07K14/50—Fibroblast growth factor [FGF]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/65—Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2
-
- 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
- C12N2799/00—Uses of viruses
- C12N2799/02—Uses of viruses as vector
- C12N2799/021—Uses of viruses as vector for the expression of a heterologous nucleic acid
- C12N2799/022—Uses of viruses as vector for the expression of a heterologous nucleic acid where the vector is derived from an adenovirus
-
- 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
- C12N2799/00—Uses of viruses
- C12N2799/02—Uses of viruses as vector
- C12N2799/021—Uses of viruses as vector for the expression of a heterologous nucleic acid
- C12N2799/025—Uses of viruses as vector for the expression of a heterologous nucleic acid where the vector is derived from a parvovirus
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Cardiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Biotechnology (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Vascular Medicine (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US43515699A | 1999-11-05 | 1999-11-05 | |
| US09/435,156 | 1999-11-05 | ||
| US60908000A | 2000-06-30 | 2000-06-30 | |
| US09/609,080 | 2000-06-30 | ||
| PCT/US2000/030345 WO2001034208A1 (fr) | 1999-11-05 | 2000-11-03 | Techniques et compositions permettant de traiter les maladies cardiovasculaires par l'administration de genes in vivo |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20020049031A true KR20020049031A (ko) | 2002-06-24 |
Family
ID=27030448
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020027005855A KR20020049031A (ko) | 1999-11-05 | 2000-11-03 | 생체내 유전자 송달에 의하여 심혈관 질환을 치료하기위한 기술 및 조성물 |
Country Status (10)
| Country | Link |
|---|---|
| EP (1) | EP1225921A1 (fr) |
| JP (1) | JP2003513942A (fr) |
| KR (1) | KR20020049031A (fr) |
| CN (1) | CN1433325A (fr) |
| AU (1) | AU784392B2 (fr) |
| CA (1) | CA2389524A1 (fr) |
| EA (1) | EA008538B1 (fr) |
| HK (1) | HK1048593A1 (fr) |
| NZ (1) | NZ546670A (fr) |
| WO (1) | WO2001034208A1 (fr) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101006106B1 (ko) * | 2009-06-04 | 2011-01-07 | 김현태 | 전·자기장 차단 전열선 |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001034208A1 (fr) * | 1999-11-05 | 2001-05-17 | The Regents Of The University Of California | Techniques et compositions permettant de traiter les maladies cardiovasculaires par l'administration de genes in vivo |
| US20030093147A1 (en) * | 2001-11-13 | 2003-05-15 | Ogle Matthew F. | Medical devices that stimulate growth factor production |
| KR100562824B1 (ko) | 2002-03-20 | 2006-03-23 | 주식회사 바이로메드 | 유전자 발현효율이 높으며 간세포 성장인자의 두 가지이형체를 동시에 발현하는 하이브리드 간세포 성장인자유전자 |
| PL195457B1 (pl) * | 2002-08-05 | 2007-09-28 | Zaklady Farm Polpharma Sa | Kaseta ekspresyjna, dwucistronowy wektor plazmidowy, środek farmaceutyczny oraz ich zastosowanie |
| CA2658628A1 (fr) * | 2006-07-25 | 2008-01-31 | Celladon Corporation | Transfusion coronaire epicardique anterograde prolongee de vecteurs viraux associes a l'adenovirus pour therapie genique |
| AU2008291296B2 (en) * | 2007-08-24 | 2014-02-06 | Julius-Maximilians-Universitat Wurzburg | Mutant double cyclized receptor peptides inhibiting beta1-adrenoceptor antibodies |
| MX2010010993A (es) | 2008-04-09 | 2010-11-05 | Viromed Co Ltd | Formulaciones liofilizadas de adn para expresion mejorada de adn de plasmido. |
| US20120141424A1 (en) * | 2009-01-07 | 2012-06-07 | Vegenics Pty Limited | Materials and Methods for the Treatment of Hypertension |
| US10155099B2 (en) | 2009-09-21 | 2018-12-18 | Cook Regentec Llc | Method for infusing stem cells |
| WO2013123094A2 (fr) * | 2012-02-14 | 2013-08-22 | The Regents Of The University Of California | Administration systémique et expression régulée des gènes à action paracrine pour les maladies cardiovasculaires et autres états |
| KR20150016970A (ko) | 2012-06-05 | 2015-02-13 | 머핀 인코포레이티드 | 세포 치료요법에 유용한 카테터 시스템 및 방법 |
| BR112016008267A2 (pt) | 2013-10-22 | 2017-10-03 | Viromed Co Ltd | Composição para prevenir ou tratar esclerose lateral amiotrófica usando duas ou mais isoformas de fator de crescimento de hepatócito |
| US20210393805A1 (en) * | 2018-05-16 | 2021-12-23 | University Of Massachusetts | Perfusion-based delivery of recombinant aav vectors for expression of secreted proteins |
| AU2019305221A1 (en) | 2018-07-19 | 2021-02-18 | Helixmith Co., Ltd. | Lyophilized pharmaceutical compositions for naked DNA gene therapy |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001034208A1 (fr) * | 1999-11-05 | 2001-05-17 | The Regents Of The University Of California | Techniques et compositions permettant de traiter les maladies cardiovasculaires par l'administration de genes in vivo |
| EP0760682A4 (fr) * | 1995-02-28 | 1998-09-09 | Univ California | Therapie angiogenique par transfert de genes |
| US5792453A (en) * | 1995-02-28 | 1998-08-11 | The Regents Of The University Of California | Gene transfer-mediated angiogenesis therapy |
| IL131021A0 (en) * | 1997-01-29 | 2001-01-28 | Cornell Res Foundation Inc | Multiple site delivery of adenoviral vector for the induction of angiogenesis |
| JP2002515065A (ja) * | 1997-05-06 | 2002-05-21 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 脈管形成トランスジーンのインビボ送達により心不全および心室再構成を処置するための技術および組成物 |
| EP1053025A2 (fr) * | 1998-02-11 | 2000-11-22 | The Regents of the University of California | Traitement de l'angiogenese par transfert de genes et techniques d'apport intravasculaire de genes |
| WO2000038518A1 (fr) * | 1998-12-28 | 2000-07-06 | Arch Development Corporation | Transfert efficace et stable in vivo de genes dans des cardiomyocytes a l'aide de vecteurs viraux adeno-associes de recombinaison |
-
2000
- 2000-11-03 WO PCT/US2000/030345 patent/WO2001034208A1/fr active Application Filing
- 2000-11-03 JP JP2001536204A patent/JP2003513942A/ja active Pending
- 2000-11-03 CA CA002389524A patent/CA2389524A1/fr not_active Abandoned
- 2000-11-03 KR KR1020027005855A patent/KR20020049031A/ko not_active Application Discontinuation
- 2000-11-03 CN CN00816481A patent/CN1433325A/zh active Pending
- 2000-11-03 NZ NZ546670A patent/NZ546670A/en not_active IP Right Cessation
- 2000-11-03 AU AU14604/01A patent/AU784392B2/en not_active Ceased
- 2000-11-03 EA EA200200533A patent/EA008538B1/ru not_active IP Right Cessation
- 2000-11-03 EP EP00976894A patent/EP1225921A1/fr not_active Withdrawn
-
2003
- 2003-01-29 HK HK03100751.6A patent/HK1048593A1/zh unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101006106B1 (ko) * | 2009-06-04 | 2011-01-07 | 김현태 | 전·자기장 차단 전열선 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1433325A (zh) | 2003-07-30 |
| CA2389524A1 (fr) | 2001-05-17 |
| EA200200533A1 (ru) | 2002-12-26 |
| AU1460401A (en) | 2001-06-06 |
| WO2001034208A1 (fr) | 2001-05-17 |
| HK1048593A1 (zh) | 2003-04-11 |
| EA008538B1 (ru) | 2007-06-29 |
| AU784392B2 (en) | 2006-03-23 |
| NZ546670A (en) | 2009-02-28 |
| EP1225921A1 (fr) | 2002-07-31 |
| JP2003513942A (ja) | 2003-04-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20090082293A1 (en) | Techniques and compositions for treating cardiovascular disease by in vivo gene delivery | |
| US6583276B1 (en) | Angiogenic factors and use thereof in treating cardiovascular disease | |
| US20080254109A1 (en) | Localized myocardial injection method for treating ischemic myocardium | |
| US20030144200A1 (en) | Novel forms of the angiogenic factor vascular endothelial cell growth factor: VEGF | |
| KR20020049031A (ko) | 생체내 유전자 송달에 의하여 심혈관 질환을 치료하기위한 기술 및 조성물 | |
| AU770384B2 (en) | Methods of altering cardiac cell phenotype | |
| CA2289600C (fr) | Techniques et compositions destinees au traitement d'une insuffisance cardiaque et du remodelage ventriculaire par apport in vivo de transgenes angiogeniques | |
| EP1695719A1 (fr) | Combinaision d'une acide nucléaire et d'un agent vasoactif pour l'amélioration de transfert de gènes | |
| WO2002002148A2 (fr) | Compositions de therapie genique renfermant deux genes recombines, et methodes d'utilisation correspondantes | |
| US20130096500A1 (en) | Nucleic acid based cardiovascular therapeutics | |
| AU2006200170B2 (en) | Combination of a nucleic acid and a vasoactive agent for enhanced gene delivery | |
| WO2009039217A1 (fr) | Médicaments pour le traitement de syndromes coronaires | |
| US20160296674A1 (en) | Nucleic acid based cardiovascular therapeutics |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A201 | Request for examination | ||
| E902 | Notification of reason for refusal | ||
| E601 | Decision to refuse application |