NZ546670A - Techniques and compositions for treating cardiovascular disease by in vivo gene delivery - Google Patents
Techniques and compositions for treating cardiovascular disease by in vivo gene delivery Download PDFInfo
- Publication number
- NZ546670A NZ546670A NZ546670A NZ54667000A NZ546670A NZ 546670 A NZ546670 A NZ 546670A NZ 546670 A NZ546670 A NZ 546670A NZ 54667000 A NZ54667000 A NZ 54667000A NZ 546670 A NZ546670 A NZ 546670A
- Authority
- NZ
- New Zealand
- Prior art keywords
- composition
- vector
- fgf
- gene
- transgene
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 59
- 238000001727 in vivo Methods 0.000 title claims description 39
- 238000000034 method Methods 0.000 title description 107
- 238000001476 gene delivery Methods 0.000 title description 32
- 208000024172 Cardiovascular disease Diseases 0.000 title description 13
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 298
- 239000013598 vector Substances 0.000 claims abstract description 205
- 108700019146 Transgenes Proteins 0.000 claims abstract description 118
- 108010074415 Angiogenic Proteins Proteins 0.000 claims abstract description 113
- 102000008076 Angiogenic Proteins Human genes 0.000 claims abstract description 111
- 230000014509 gene expression Effects 0.000 claims abstract description 84
- 230000002491 angiogenic effect Effects 0.000 claims abstract description 58
- 238000001415 gene therapy Methods 0.000 claims abstract description 30
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 claims abstract description 5
- 102000009840 Angiopoietins Human genes 0.000 claims abstract description 4
- 108010009906 Angiopoietins Proteins 0.000 claims abstract description 4
- 206010021143 Hypoxia Diseases 0.000 claims abstract description 4
- 102000008299 Nitric Oxide Synthase Human genes 0.000 claims abstract description 3
- 108010021487 Nitric Oxide Synthase Proteins 0.000 claims abstract description 3
- 108010088577 zinc-binding protein Proteins 0.000 claims abstract description 3
- 241000701161 unidentified adenovirus Species 0.000 claims description 104
- 238000002347 injection Methods 0.000 claims description 69
- 239000007924 injection Substances 0.000 claims description 69
- 238000012384 transportation and delivery Methods 0.000 claims description 69
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 claims description 52
- 239000013603 viral vector Substances 0.000 claims description 33
- 108010076504 Protein Sorting Signals Proteins 0.000 claims description 31
- 239000002245 particle Substances 0.000 claims description 29
- 210000001367 artery Anatomy 0.000 claims description 28
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 28
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims description 27
- 102000013275 Somatomedins Human genes 0.000 claims description 26
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 claims description 24
- 210000004204 blood vessel Anatomy 0.000 claims description 24
- 210000004413 cardiac myocyte Anatomy 0.000 claims description 24
- 239000002550 vasoactive agent Substances 0.000 claims description 23
- 230000010076 replication Effects 0.000 claims description 18
- 102000018233 Fibroblast Growth Factor Human genes 0.000 claims description 14
- 108050007372 Fibroblast Growth Factor Proteins 0.000 claims description 14
- 239000002840 nitric oxide donor Substances 0.000 claims description 14
- 230000002950 deficient Effects 0.000 claims description 13
- 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 claims description 13
- 229940126864 fibroblast growth factor Drugs 0.000 claims description 13
- 238000001802 infusion Methods 0.000 claims description 13
- 229940083618 sodium nitroprusside Drugs 0.000 claims description 13
- 150000002632 lipids Chemical class 0.000 claims description 10
- 108010067390 Viral Proteins Proteins 0.000 claims description 8
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 claims description 6
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 claims description 6
- 102000005604 Myosin Heavy Chains Human genes 0.000 claims description 5
- 108010084498 Myosin Heavy Chains Proteins 0.000 claims description 5
- 102000016349 Myosin Light Chains Human genes 0.000 claims description 5
- 108010067385 Myosin Light Chains Proteins 0.000 claims description 5
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims description 5
- 238000001361 intraarterial administration Methods 0.000 claims description 4
- 238000010255 intramuscular injection Methods 0.000 claims description 4
- 239000007927 intramuscular injection Substances 0.000 claims description 4
- 108091006024 signal transducing proteins Proteins 0.000 claims description 3
- 102000034285 signal transducing proteins Human genes 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- BHMLFPOTZYRDKA-IRXDYDNUSA-N (2s)-2-[(s)-(2-iodophenoxy)-phenylmethyl]morpholine Chemical compound IC1=CC=CC=C1O[C@@H](C=1C=CC=CC=1)[C@H]1OCCNC1 BHMLFPOTZYRDKA-IRXDYDNUSA-N 0.000 claims 1
- 102100021866 Hepatocyte growth factor Human genes 0.000 claims 1
- 229940124531 pharmaceutical excipient Drugs 0.000 claims 1
- 102000003745 Hepatocyte Growth Factor Human genes 0.000 abstract description 4
- 238000012546 transfer Methods 0.000 description 154
- 210000004027 cell Anatomy 0.000 description 126
- 230000017531 blood circulation Effects 0.000 description 116
- 241001465754 Metazoa Species 0.000 description 114
- 210000002216 heart Anatomy 0.000 description 97
- 108090000380 Fibroblast growth factor 5 Proteins 0.000 description 77
- 210000001519 tissue Anatomy 0.000 description 72
- 210000004165 myocardium Anatomy 0.000 description 64
- 206010019280 Heart failures Diseases 0.000 description 60
- 102100028073 Fibroblast growth factor 5 Human genes 0.000 description 59
- 102000004169 proteins and genes Human genes 0.000 description 53
- 230000002861 ventricular Effects 0.000 description 53
- 230000002107 myocardial effect Effects 0.000 description 51
- 210000004351 coronary vessel Anatomy 0.000 description 46
- 230000003612 virological effect Effects 0.000 description 46
- 230000000302 ischemic effect Effects 0.000 description 43
- 230000006870 function Effects 0.000 description 41
- 206010007559 Cardiac failure congestive Diseases 0.000 description 38
- 230000001965 increasing effect Effects 0.000 description 38
- 241000700605 Viruses Species 0.000 description 37
- 108090000381 Fibroblast growth factor 4 Proteins 0.000 description 36
- 230000033115 angiogenesis Effects 0.000 description 36
- 102100028072 Fibroblast growth factor 4 Human genes 0.000 description 33
- 230000000694 effects Effects 0.000 description 33
- 239000013612 plasmid Substances 0.000 description 32
- 101150066555 lacZ gene Proteins 0.000 description 31
- 108091033319 polynucleotide Proteins 0.000 description 31
- 102000040430 polynucleotide Human genes 0.000 description 31
- 239000002157 polynucleotide Substances 0.000 description 31
- 230000004087 circulation Effects 0.000 description 30
- 208000019622 heart disease Diseases 0.000 description 30
- 208000031225 myocardial ischemia Diseases 0.000 description 28
- 230000008719 thickening Effects 0.000 description 28
- 108010016628 ameroid Proteins 0.000 description 27
- 201000010046 Dilated cardiomyopathy Diseases 0.000 description 26
- 230000001976 improved effect Effects 0.000 description 26
- 206010056370 Congestive cardiomyopathy Diseases 0.000 description 25
- 230000000747 cardiac effect Effects 0.000 description 24
- 208000024891 symptom Diseases 0.000 description 24
- 108020004414 DNA Proteins 0.000 description 23
- 210000001736 capillary Anatomy 0.000 description 23
- 238000011282 treatment Methods 0.000 description 23
- 238000003752 polymerase chain reaction Methods 0.000 description 22
- 230000002792 vascular Effects 0.000 description 22
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 21
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 21
- 102000009524 Vascular Endothelial Growth Factor A Human genes 0.000 description 21
- 208000010125 myocardial infarction Diseases 0.000 description 21
- 208000028867 ischemia Diseases 0.000 description 20
- 101150021185 FGF gene Proteins 0.000 description 19
- 241000282898 Sus scrofa Species 0.000 description 18
- 210000004369 blood Anatomy 0.000 description 18
- 239000008280 blood Substances 0.000 description 18
- 230000001746 atrial effect Effects 0.000 description 17
- 230000010412 perfusion Effects 0.000 description 17
- 230000002093 peripheral effect Effects 0.000 description 17
- 230000008828 contractile function Effects 0.000 description 16
- 108010048367 enhanced green fluorescent protein Proteins 0.000 description 16
- 238000005259 measurement Methods 0.000 description 16
- 210000002027 skeletal muscle Anatomy 0.000 description 16
- 230000001225 therapeutic effect Effects 0.000 description 16
- 239000013607 AAV vector Substances 0.000 description 15
- 108091026890 Coding region Proteins 0.000 description 15
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 15
- 208000033774 Ventricular Remodeling Diseases 0.000 description 15
- 238000004458 analytical method Methods 0.000 description 15
- 239000000835 fiber Substances 0.000 description 15
- 239000012634 fragment Substances 0.000 description 15
- 210000005240 left ventricle Anatomy 0.000 description 15
- 102000004196 processed proteins & peptides Human genes 0.000 description 15
- 210000005166 vasculature Anatomy 0.000 description 15
- 238000011161 development Methods 0.000 description 14
- 230000018109 developmental process Effects 0.000 description 14
- 230000009467 reduction Effects 0.000 description 14
- 208000018262 Peripheral vascular disease Diseases 0.000 description 13
- 230000004064 dysfunction Effects 0.000 description 13
- 210000004185 liver Anatomy 0.000 description 13
- 230000028327 secretion Effects 0.000 description 13
- AIYUHDOJVYHVIT-UHFFFAOYSA-M caesium chloride Chemical compound [Cl-].[Cs+] AIYUHDOJVYHVIT-UHFFFAOYSA-M 0.000 description 12
- 230000008859 change Effects 0.000 description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 12
- 230000000977 initiatory effect Effects 0.000 description 12
- 241001135569 Human adenovirus 5 Species 0.000 description 11
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 11
- 201000010099 disease Diseases 0.000 description 11
- 238000002592 echocardiography Methods 0.000 description 11
- 230000004217 heart function Effects 0.000 description 11
- 238000004519 manufacturing process Methods 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
- 239000003795 chemical substances by application Substances 0.000 description 10
- 208000029078 coronary artery disease Diseases 0.000 description 10
- 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 10
- 229960001340 histamine Drugs 0.000 description 10
- 239000004005 microsphere Substances 0.000 description 10
- 239000002953 phosphate buffered saline Substances 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 238000000746 purification Methods 0.000 description 10
- 230000004895 regional blood flow Effects 0.000 description 10
- 239000011780 sodium chloride Substances 0.000 description 10
- 238000007492 two-way ANOVA Methods 0.000 description 10
- 206010061218 Inflammation Diseases 0.000 description 9
- 241000282887 Suidae Species 0.000 description 9
- 238000010171 animal model Methods 0.000 description 9
- 210000000709 aorta Anatomy 0.000 description 9
- 238000013459 approach Methods 0.000 description 9
- 230000003247 decreasing effect Effects 0.000 description 9
- 230000002939 deleterious effect Effects 0.000 description 9
- 230000000004 hemodynamic effect Effects 0.000 description 9
- 230000004054 inflammatory process Effects 0.000 description 9
- 239000003550 marker Substances 0.000 description 9
- 230000001404 mediated effect Effects 0.000 description 9
- 229920001184 polypeptide Polymers 0.000 description 9
- 210000001147 pulmonary artery Anatomy 0.000 description 9
- 239000013605 shuttle vector Substances 0.000 description 9
- 238000001356 surgical procedure Methods 0.000 description 9
- 238000013518 transcription Methods 0.000 description 9
- 230000035897 transcription Effects 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 241000282412 Homo Species 0.000 description 8
- 206010020880 Hypertrophy Diseases 0.000 description 8
- 206010061216 Infarction Diseases 0.000 description 8
- 108020005202 Viral DNA Proteins 0.000 description 8
- 230000008901 benefit Effects 0.000 description 8
- 230000010339 dilation Effects 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 239000003623 enhancer Substances 0.000 description 8
- 230000006872 improvement Effects 0.000 description 8
- 230000007574 infarction Effects 0.000 description 8
- 210000003205 muscle Anatomy 0.000 description 8
- 210000000107 myocyte Anatomy 0.000 description 8
- 230000000750 progressive effect Effects 0.000 description 8
- 241000700159 Rattus Species 0.000 description 7
- 230000037396 body weight Effects 0.000 description 7
- 230000002708 enhancing effect Effects 0.000 description 7
- 230000002169 extracardiac Effects 0.000 description 7
- 230000001939 inductive effect Effects 0.000 description 7
- 208000015181 infectious disease Diseases 0.000 description 7
- 108020004999 messenger RNA Proteins 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 230000002685 pulmonary effect Effects 0.000 description 7
- 210000002966 serum Anatomy 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 238000005199 ultracentrifugation Methods 0.000 description 7
- 108090000386 Fibroblast Growth Factor 1 Proteins 0.000 description 6
- 102100031706 Fibroblast growth factor 1 Human genes 0.000 description 6
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 6
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 description 6
- 206010028851 Necrosis Diseases 0.000 description 6
- 238000000540 analysis of variance Methods 0.000 description 6
- 230000000157 blood function Effects 0.000 description 6
- 230000001413 cellular effect Effects 0.000 description 6
- 230000006735 deficit Effects 0.000 description 6
- 210000004072 lung Anatomy 0.000 description 6
- 230000017074 necrotic cell death Effects 0.000 description 6
- 235000015097 nutrients Nutrition 0.000 description 6
- 230000008488 polyadenylation Effects 0.000 description 6
- 230000000644 propagated effect Effects 0.000 description 6
- 230000006798 recombination Effects 0.000 description 6
- 238000005215 recombination Methods 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 210000001525 retina Anatomy 0.000 description 6
- 230000000250 revascularization Effects 0.000 description 6
- 230000003248 secreting effect Effects 0.000 description 6
- 230000008685 targeting Effects 0.000 description 6
- 238000001890 transfection Methods 0.000 description 6
- 241001430294 unidentified retrovirus Species 0.000 description 6
- 201000001320 Atherosclerosis Diseases 0.000 description 5
- 208000000059 Dyspnea Diseases 0.000 description 5
- 206010013975 Dyspnoeas Diseases 0.000 description 5
- 208000009525 Myocarditis Diseases 0.000 description 5
- 206010030113 Oedema 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
- 230000009286 beneficial effect Effects 0.000 description 5
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 5
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 5
- 238000004113 cell culture Methods 0.000 description 5
- 239000002299 complementary DNA Substances 0.000 description 5
- 230000002596 correlated effect Effects 0.000 description 5
- 230000000875 corresponding effect Effects 0.000 description 5
- 230000001747 exhibiting effect Effects 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 239000003453 histamine agonist Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 210000004962 mammalian cell Anatomy 0.000 description 5
- 210000001349 mammary artery Anatomy 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 230000002503 metabolic effect Effects 0.000 description 5
- 238000000424 optical density measurement Methods 0.000 description 5
- 238000004806 packaging method and process Methods 0.000 description 5
- 239000013641 positive control Substances 0.000 description 5
- 230000035755 proliferation Effects 0.000 description 5
- 210000003752 saphenous vein Anatomy 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
- 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 4
- 200000000007 Arterial disease Diseases 0.000 description 4
- 206010003445 Ascites Diseases 0.000 description 4
- 102000016911 Deoxyribonucleases Human genes 0.000 description 4
- 108010053770 Deoxyribonucleases Proteins 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
- 238000010162 Tukey test Methods 0.000 description 4
- 208000009982 Ventricular Dysfunction Diseases 0.000 description 4
- 125000003275 alpha amino acid group Chemical group 0.000 description 4
- 238000002399 angioplasty Methods 0.000 description 4
- 230000000692 anti-sense effect Effects 0.000 description 4
- 208000028922 artery disease Diseases 0.000 description 4
- 230000027455 binding Effects 0.000 description 4
- 230000036770 blood supply Effects 0.000 description 4
- 108091092356 cellular DNA Proteins 0.000 description 4
- 210000000038 chest Anatomy 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 4
- 238000010367 cloning Methods 0.000 description 4
- 238000010276 construction Methods 0.000 description 4
- 239000002872 contrast media Substances 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
- 239000012530 fluid Substances 0.000 description 4
- 102000058223 human VEGFA Human genes 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 238000010348 incorporation Methods 0.000 description 4
- 210000005246 left atrium Anatomy 0.000 description 4
- 239000002502 liposome Substances 0.000 description 4
- 230000007774 longterm Effects 0.000 description 4
- 229920002521 macromolecule Polymers 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 238000007431 microscopic evaluation Methods 0.000 description 4
- 210000000663 muscle cell Anatomy 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 238000011422 pharmacological therapy Methods 0.000 description 4
- 238000007634 remodeling Methods 0.000 description 4
- 230000003362 replicative effect Effects 0.000 description 4
- 210000005241 right ventricle Anatomy 0.000 description 4
- 238000010561 standard procedure Methods 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- 230000009885 systemic effect Effects 0.000 description 4
- 238000010361 transduction Methods 0.000 description 4
- 230000026683 transduction Effects 0.000 description 4
- 230000006815 ventricular dysfunction Effects 0.000 description 4
- 238000001262 western blot Methods 0.000 description 4
- 241000282472 Canis lupus familiaris Species 0.000 description 3
- 206010007558 Cardiac failure chronic Diseases 0.000 description 3
- 208000006029 Cardiomegaly Diseases 0.000 description 3
- 102000053602 DNA Human genes 0.000 description 3
- 230000006820 DNA synthesis Effects 0.000 description 3
- 241000702421 Dependoparvovirus Species 0.000 description 3
- 108090000382 Fibroblast growth factor 6 Proteins 0.000 description 3
- 206010016654 Fibrosis Diseases 0.000 description 3
- 241000288140 Gruiformes Species 0.000 description 3
- 101100446512 Homo sapiens FGF4 gene Proteins 0.000 description 3
- 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 102100026827 Protein associated with UVRAG as autophagy enhancer Human genes 0.000 description 3
- 101710102978 Protein associated with UVRAG as autophagy enhancer Proteins 0.000 description 3
- 208000037656 Respiratory Sounds Diseases 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
- 230000002411 adverse Effects 0.000 description 3
- 210000004102 animal cell Anatomy 0.000 description 3
- 230000004872 arterial blood pressure Effects 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 210000001054 cardiac fibroblast Anatomy 0.000 description 3
- 210000001715 carotid artery Anatomy 0.000 description 3
- 230000003915 cell function Effects 0.000 description 3
- 210000000349 chromosome Anatomy 0.000 description 3
- 230000008602 contraction Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 230000029087 digestion Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003937 drug carrier Substances 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
- 210000001508 eye Anatomy 0.000 description 3
- 210000001105 femoral artery Anatomy 0.000 description 3
- 210000002950 fibroblast Anatomy 0.000 description 3
- 230000004761 fibrosis Effects 0.000 description 3
- -1 for example Proteins 0.000 description 3
- 229930182830 galactose Natural products 0.000 description 3
- 210000005003 heart tissue Anatomy 0.000 description 3
- 238000003384 imaging method Methods 0.000 description 3
- 230000028993 immune response Effects 0.000 description 3
- 230000001771 impaired effect Effects 0.000 description 3
- 210000004969 inflammatory cell Anatomy 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 230000028709 inflammatory response Effects 0.000 description 3
- 238000007689 inspection Methods 0.000 description 3
- 208000010729 leg swelling Diseases 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000010016 myocardial function Effects 0.000 description 3
- 239000013642 negative control 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 group 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 230000002085 persistent effect Effects 0.000 description 3
- 229960001802 phenylephrine Drugs 0.000 description 3
- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 3
- 230000004962 physiological condition Effects 0.000 description 3
- 238000013310 pig model Methods 0.000 description 3
- 101150086745 pre gene Proteins 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000004393 prognosis Methods 0.000 description 3
- 206010037833 rales Diseases 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 230000036387 respiratory rate Effects 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 238000005070 sampling Methods 0.000 description 3
- 239000012679 serum free medium Substances 0.000 description 3
- 238000004904 shortening Methods 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 230000002459 sustained effect Effects 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 238000002054 transplantation Methods 0.000 description 3
- 238000011144 upstream manufacturing Methods 0.000 description 3
- 230000008728 vascular permeability Effects 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
- WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 2
- 239000005541 ACE inhibitor Substances 0.000 description 2
- 102100030988 Angiotensin-converting enzyme Human genes 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 208000020446 Cardiac disease Diseases 0.000 description 2
- 206010065929 Cardiovascular insufficiency Diseases 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- 208000001778 Coronary Occlusion Diseases 0.000 description 2
- 206010011086 Coronary artery occlusion 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
- 102000052510 DNA-Binding Proteins Human genes 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
- 241000713800 Feline immunodeficiency virus Species 0.000 description 2
- 102100028075 Fibroblast growth factor 6 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
- 102100037852 Insulin-like growth factor I Human genes 0.000 description 2
- 241000713666 Lentivirus Species 0.000 description 2
- 238000000134 MTT assay Methods 0.000 description 2
- 231100000002 MTT assay Toxicity 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 101001055320 Myxine glutinosa Insulin-like growth factor Proteins 0.000 description 2
- 238000011887 Necropsy Methods 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 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
- 206010047281 Ventricular arrhythmia Diseases 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 230000006978 adaptation Effects 0.000 description 2
- 230000008649 adaptation response Effects 0.000 description 2
- GFFGJBXGBJISGV-UHFFFAOYSA-N adenyl group Chemical class N1=CN=C2N=CNC2=C1N GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 2
- 102000030621 adenylate cyclase Human genes 0.000 description 2
- 108060000200 adenylate cyclase Proteins 0.000 description 2
- 230000001800 adrenalinergic effect Effects 0.000 description 2
- 239000000674 adrenergic antagonist Substances 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 2
- 102000005936 beta-Galactosidase Human genes 0.000 description 2
- 108010005774 beta-Galactosidase Proteins 0.000 description 2
- 230000001588 bifunctional effect Effects 0.000 description 2
- 238000001574 biopsy Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000008366 buffered solution Substances 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 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
- 238000012761 co-transfection Methods 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
- 239000000356 contaminant Substances 0.000 description 2
- 210000003748 coronary sinus Anatomy 0.000 description 2
- 238000000502 dialysis Methods 0.000 description 2
- 230000003205 diastolic effect Effects 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 230000006806 disease prevention Effects 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 239000002934 diuretic Substances 0.000 description 2
- 229940030606 diuretics Drugs 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 239000000839 emulsion Substances 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
- 230000012010 growth Effects 0.000 description 2
- 210000002064 heart cell Anatomy 0.000 description 2
- 229960002897 heparin Drugs 0.000 description 2
- 229920000669 heparin Polymers 0.000 description 2
- 238000003119 immunoblot Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000010354 integration Effects 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 238000001638 lipofection Methods 0.000 description 2
- 230000004807 localization Effects 0.000 description 2
- 210000003141 lower extremity Anatomy 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 239000000693 micelle Substances 0.000 description 2
- 238000000386 microscopy Methods 0.000 description 2
- 230000002438 mitochondrial effect Effects 0.000 description 2
- 230000002297 mitogenic effect 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
- 210000000056 organ Anatomy 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
- 230000036961 partial effect Effects 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 230000000737 periodic effect Effects 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 238000010837 poor prognosis Methods 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 239000013608 rAAV vector Substances 0.000 description 2
- 239000002331 radioactive microsphere Substances 0.000 description 2
- 238000011552 rat model Methods 0.000 description 2
- 102000037983 regulatory factors Human genes 0.000 description 2
- 108091008025 regulatory factors Proteins 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000002103 transcriptional effect Effects 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- 238000010967 transthoracic echocardiography Methods 0.000 description 2
- 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 2
- 210000002700 urine Anatomy 0.000 description 2
- 238000007631 vascular surgery Methods 0.000 description 2
- 230000007998 vessel formation Effects 0.000 description 2
- 230000029812 viral genome replication Effects 0.000 description 2
- 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
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-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
- 238000010600 3H thymidine incorporation assay Methods 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
- 229920000936 Agarose Polymers 0.000 description 1
- 206010003210 Arteriosclerosis 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
- WOVKYSAHUYNSMH-UHFFFAOYSA-N BROMODEOXYURIDINE Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-UHFFFAOYSA-N 0.000 description 1
- 101100450705 Caenorhabditis elegans hif-1 gene Proteins 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 206010007556 Cardiac failure acute Diseases 0.000 description 1
- 208000031229 Cardiomyopathies Diseases 0.000 description 1
- 206010048610 Cardiotoxicity Diseases 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 241001432959 Chernes Species 0.000 description 1
- 206010008479 Chest Pain Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 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
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 201000000054 Coronary Restenosis Diseases 0.000 description 1
- 201000000057 Coronary Stenosis 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
- 102000012410 DNA Ligases Human genes 0.000 description 1
- 108010061982 DNA Ligases Proteins 0.000 description 1
- 108700020911 DNA-Binding Proteins Proteins 0.000 description 1
- 101710096438 DNA-binding protein Proteins 0.000 description 1
- 208000034423 Delivery Diseases 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
- 102100031780 Endonuclease Human genes 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
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 206010053487 Exposure to toxic agent Diseases 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
- 102000002464 Galactosidases Human genes 0.000 description 1
- 108010093031 Galactosidases 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
- 239000007995 HEPES buffer Substances 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
- 241000701131 Human adenovirus 14 Species 0.000 description 1
- 241000701024 Human betaherpesvirus 5 Species 0.000 description 1
- 241000725303 Human immunodeficiency virus 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
- 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
- 108090000362 Lymphotoxin-beta Proteins 0.000 description 1
- 241001529936 Murinae Species 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
- 238000010222 PCR analysis Methods 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 1
- 206010034576 Peripheral ischaemia Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 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
- 206010038389 Renal cancer Diseases 0.000 description 1
- 241000220010 Rhode Species 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 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
- 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 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 102000013534 Troponin C Human genes 0.000 description 1
- 108010073925 Vascular Endothelial Growth Factor B Proteins 0.000 description 1
- 102000009520 Vascular Endothelial Growth Factor C Human genes 0.000 description 1
- 108010073923 Vascular Endothelial Growth Factor C Proteins 0.000 description 1
- 102100038217 Vascular endothelial growth factor B Human genes 0.000 description 1
- 206010047295 Ventricular hypertrophy 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
- 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
- 210000001015 abdomen 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
- 230000004913 activation Effects 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 108700010877 adenoviridae proteins Proteins 0.000 description 1
- 239000000808 adrenergic beta-agonist Substances 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
- 230000004075 alteration Effects 0.000 description 1
- 230000001668 ameliorated effect Effects 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
- 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
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 210000000702 aorta abdominal Anatomy 0.000 description 1
- 210000002565 arteriole Anatomy 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 229960002028 atropine sulfate Drugs 0.000 description 1
- 230000003190 augmentative effect Effects 0.000 description 1
- 238000010009 beating Methods 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
- UUQMNUMQCIQDMZ-UHFFFAOYSA-N betahistine Chemical compound CNCCC1=CC=CC=N1 UUQMNUMQCIQDMZ-UHFFFAOYSA-N 0.000 description 1
- 229960004536 betahistine Drugs 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015624 blood vessel development 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
- 229950004398 broxuridine Drugs 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 239000007978 cacodylate buffer Substances 0.000 description 1
- 239000000480 calcium channel blocker Substances 0.000 description 1
- 238000004364 calculation method Methods 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
- 230000030833 cell death Effects 0.000 description 1
- 230000003822 cell turnover Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000003636 conditioned culture medium Substances 0.000 description 1
- 230000009091 contractile dysfunction Effects 0.000 description 1
- 230000009989 contractile response Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000012937 correction Methods 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
- 238000011461 current therapy Methods 0.000 description 1
- 238000005520 cutting process Methods 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
- 230000007812 deficiency Effects 0.000 description 1
- 238000002716 delivery method Methods 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
- 238000013461 design Methods 0.000 description 1
- 230000006866 deterioration 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
- 230000004069 differentiation Effects 0.000 description 1
- 108010060984 digitalis receptor Proteins 0.000 description 1
- 230000000916 dilatatory effect Effects 0.000 description 1
- 201000011304 dilated cardiomyopathy 1A Diseases 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 230000001667 episodic effect Effects 0.000 description 1
- 230000003090 exacerbative effect Effects 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 238000013213 extrapolation Methods 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
- 238000000684 flow cytometry Methods 0.000 description 1
- 238000000799 fluorescence microscopy Methods 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
- 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
- 239000003102 growth factor Substances 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
- 230000009931 harmful effect Effects 0.000 description 1
- 230000005986 heart dysfunction Effects 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 238000004128 high performance liquid chromatography 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
- 210000003090 iliac artery Anatomy 0.000 description 1
- 238000003365 immunocytochemistry Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000013101 initial test Methods 0.000 description 1
- 239000004041 inotropic agent Substances 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 229960003299 ketamine Drugs 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 238000011542 limb amputation Methods 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 210000004880 lymph fluid Anatomy 0.000 description 1
- 239000006166 lysate Substances 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
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000013160 medical therapy Methods 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
- 210000001589 microsome Anatomy 0.000 description 1
- 239000006151 minimal media Substances 0.000 description 1
- 230000008747 mitogenic response Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000010369 molecular cloning 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
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 108010067198 mutein 2 Proteins 0.000 description 1
- 208000037891 myocardial injury Diseases 0.000 description 1
- 208000002089 myocardial stunning Diseases 0.000 description 1
- 230000003274 myotonic 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
- 231100001083 no cytotoxicity 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
- 230000001151 other effect Effects 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 229960001789 papaverine Drugs 0.000 description 1
- 210000003540 papillary muscle Anatomy 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 210000003516 pericardium Anatomy 0.000 description 1
- 206010049430 peripartum cardiomyopathy Diseases 0.000 description 1
- 230000036581 peripheral resistance Effects 0.000 description 1
- 210000003200 peritoneal cavity Anatomy 0.000 description 1
- 239000002831 pharmacologic agent Substances 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
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 230000006461 physiological response Effects 0.000 description 1
- 108010017843 platelet-derived growth factor A Proteins 0.000 description 1
- 229920000642 polymer Polymers 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
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 230000003334 potential effect Effects 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
- 230000002265 prevention Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000000718 qrs complex Methods 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 210000001567 regular cardiac muscle cell of ventricle Anatomy 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 201000010174 renal carcinoma Diseases 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 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
- 230000000717 retained effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 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
- 230000019491 signal transduction Effects 0.000 description 1
- 230000037432 silent mutation Effects 0.000 description 1
- 210000002460 smooth muscle Anatomy 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
- 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
- BNHGKKNINBGEQL-UHFFFAOYSA-M sodium;5-ethyl-5-(3-methylbutyl)pyrimidin-3-ide-2,4,6-trione Chemical compound [Na+].CC(C)CCC1(CC)C(=O)NC(=O)[N-]C1=O BNHGKKNINBGEQL-UHFFFAOYSA-M 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 208000014221 sudden cardiac arrest Diseases 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000011477 surgical intervention Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- 208000008203 tachypnea Diseases 0.000 description 1
- 206010043089 tachypnoea Diseases 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000002627 tracheal intubation Methods 0.000 description 1
- 230000009261 transgenic effect Effects 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
- 238000012285 ultrasound imaging Methods 0.000 description 1
- 210000001604 vasa vasorum Anatomy 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 210000000264 venule Anatomy 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 210000002845 virion Anatomy 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
- 230000003442 weekly effect Effects 0.000 description 1
- 238000005303 weighing Methods 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)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Biotechnology (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Diabetes (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Endocrinology (AREA)
- Hospice & Palliative Care (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 (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US43515699A | 1999-11-05 | 1999-11-05 | |
US60908000A | 2000-06-30 | 2000-06-30 |
Publications (1)
Publication Number | Publication Date |
---|---|
NZ546670A true NZ546670A (en) | 2009-02-28 |
Family
ID=27030448
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NZ546670A NZ546670A (en) | 1999-11-05 | 2000-11-03 | Techniques and compositions for treating cardiovascular disease by in vivo gene delivery |
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) |
Families Citing this family (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NZ546670A (en) * | 1999-11-05 | 2009-02-28 | Univ California | Techniques and compositions for treating cardiovascular disease by in vivo gene delivery |
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 |
DK2197900T3 (da) * | 2007-08-24 | 2012-10-22 | Univ Wuerzburg J Maximilians | Mutante dobbeltringsluttede receptorpeptider, der inhiberer beta1-adrenoreceptorantistoffer |
CA2720611C (fr) | 2008-04-09 | 2016-07-12 | Viromed Co., Ltd. | Formulations lyophilisees d'adn pour une expression amelioree d'un adn plasmidique |
EP2385840A4 (fr) * | 2009-01-07 | 2012-12-12 | Vegenics Pty Ltd | Matériaux et méthodes pour le traitement de l' hypertension |
KR101006106B1 (ko) * | 2009-06-04 | 2011-01-07 | 김현태 | 전·자기장 차단 전열선 |
US10155099B2 (en) | 2009-09-21 | 2018-12-18 | Cook Regentec Llc | Method for infusing stem cells |
PL2814513T3 (pl) * | 2012-02-14 | 2018-06-29 | The Regents Of The University Of California | Układowe dostarczanie i regulowana ekspresja genów parakrynnych w chorobach sercowo-naczyniowych i innych stanach |
US9604037B2 (en) | 2012-06-05 | 2017-03-28 | Muffin Incorporated | Catheter systems and methods useful for cell therapy |
US10639351B2 (en) | 2013-10-22 | 2020-05-05 | Helixmith Co., Ltd. | Method for treating amyotrophic lateral sclerosis with a polynucleotide encoding two or more isoforms of hepatocyte growth factor |
WO2019222455A1 (fr) * | 2018-05-16 | 2019-11-21 | University Of Massachusetts | Administration à base de perfusion de vecteurs de vaa recombinés pour l'expression de protéines sécrétées |
US11554179B2 (en) | 2018-07-19 | 2023-01-17 | Helixmith Co., Ltd | Lyophilized pharmaceutical compositions for naked DNA gene therapy |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5792453A (en) * | 1995-02-28 | 1998-08-11 | The Regents Of The University Of California | Gene transfer-mediated angiogenesis therapy |
CN100569297C (zh) * | 1995-02-28 | 2009-12-16 | 加利福尼亚大学董事会 | 基因转移介导的血管形成疗法 |
IL131021A0 (en) * | 1997-01-29 | 2001-01-28 | Cornell Res Foundation Inc | Multiple site delivery of adenoviral vector for the induction of angiogenesis |
WO1998050079A2 (fr) * | 1997-05-06 | 1998-11-12 | The Regents Of The University Of California | Techniques et compositions destinees au traitement d'une insuffisance cardiaque et du remodelage ventriculaire par apport in vivo de transgenes angiogeniques |
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 |
NZ546670A (en) * | 1999-11-05 | 2009-02-28 | Univ California | Techniques and compositions for treating cardiovascular disease by in vivo gene delivery |
-
2000
- 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 CN CN00816481A patent/CN1433325A/zh active Pending
- 2000-11-03 EP EP00976894A patent/EP1225921A1/fr not_active Withdrawn
- 2000-11-03 EA EA200200533A patent/EA008538B1/ru not_active IP Right Cessation
- 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 WO PCT/US2000/030345 patent/WO2001034208A1/fr active Application Filing
-
2003
- 2003-01-29 HK HK03100751.6A patent/HK1048593A1/zh unknown
Also Published As
Publication number | Publication date |
---|---|
AU784392B2 (en) | 2006-03-23 |
CN1433325A (zh) | 2003-07-30 |
WO2001034208A1 (fr) | 2001-05-17 |
CA2389524A1 (fr) | 2001-05-17 |
EP1225921A1 (fr) | 2002-07-31 |
EA008538B1 (ru) | 2007-06-29 |
JP2003513942A (ja) | 2003-04-15 |
EA200200533A1 (ru) | 2002-12-26 |
KR20020049031A (ko) | 2002-06-24 |
HK1048593A1 (zh) | 2003-04-11 |
AU1460401A (en) | 2001-06-06 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20090082293A1 (en) | Techniques and compositions for treating cardiovascular disease by in vivo gene delivery | |
AU706908B2 (en) | Gene-transfer-mediated angiogenesis therapy | |
US6174871B1 (en) | Gene therapies for enhancing cardiac function | |
AU784392B2 (en) | Techniques and compositions for treating cardiovascular disease by in vivo gene delivery | |
CA2289600C (fr) | Techniques et compositions destinees au traitement d'une insuffisance cardiaque et du remodelage ventriculaire par apport in vivo de transgenes angiogeniques | |
WO1999062940A9 (fr) | Procedes de modification du phenotype de la cellule cardiaque | |
EP1695719A1 (fr) | Combinaision d'une acide nucléaire et d'un agent vasoactif pour l'amélioration de transfert de gènes | |
AU2002216751A1 (en) | Dual recombinant gene therapy compositions and methods of use | |
US20130096500A1 (en) | Nucleic acid based cardiovascular therapeutics | |
AU2006200170B2 (en) | Combination of a nucleic acid and a vasoactive agent for enhanced gene delivery | |
AU706050C (en) | Gene transfer-mediated angiogenesis therapy | |
US20160296674A1 (en) | Nucleic acid based cardiovascular therapeutics | |
AU2006235836A1 (en) | Gene transfer-mediated angiogenesis therapy | |
AU4754199A (en) | Gene transfer-mediated angiogenesis therapy |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PSEA | Patent sealed | ||
RENW | Renewal (renewal fees accepted) | ||
RENW | Renewal (renewal fees accepted) | ||
RENW | Renewal (renewal fees accepted) |
Free format text: PATENT RENEWED FOR 7 YEARS UNTIL 03 NOV 2020 BY COMPUTER PACKAGES INC Effective date: 20131126 |
|
EXPY | Patent expired |