Baculovirus-mediated vascular endothelial growth factor-DΔNΔC gene transfer induces angiogenesis in rabbit skeletal muscle
Background Occluded arteries and ischemic tissues cannot always be treated by angioplasty, stenting or by‐pass‐surgery. Under such circumstances, viral gene therapy may be useful in inducing increased blood supply to ischemic area. There is evidence of improved blood flow in ischemic skeletal muscle...
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Published in | The journal of gene medicine Vol. 14; no. 1; pp. 35 - 43 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Chichester, UK
John Wiley & Sons, Ltd
01.01.2012
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Subjects | |
Online Access | Get full text |
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Abstract | Background
Occluded arteries and ischemic tissues cannot always be treated by angioplasty, stenting or by‐pass‐surgery. Under such circumstances, viral gene therapy may be useful in inducing increased blood supply to ischemic area. There is evidence of improved blood flow in ischemic skeletal muscle and myocardium in both animal and human studies using adenoviral vascular endothelial growth factor (VEGF) gene therapy. However, the expression is transient and repeated gene transfers with the same vector are inefficient due to immune responses.
Methods
Different baculoviral vectors pseudotyped with or without vesicular stomatitis virus glycoprotein (VSV‐G) and/or carrying woodchuck hepatitis virus post‐transcriptional regulatory element (Wpre) were tested both in vitro and in vivo. VEGF‐DΔNΔC was used as therapeutic transgene and lacZ as a control. In vivo efficacy was evaluated as capillary enlargement and transgene expression in New Zealand White (NZW) rabbit skeletal muscle.
Results
A statistically significant capillary enlargement was detected 6 days after gene transfer in transduced areas compared to the control gene transfers with baculovirus and adenovirus encoding β‐galactosidase (lacZ). Substantially improved gene transfer efficiency was achieved with a modified baculovirus pseudotyped with VSV‐G and carrying Wpre. Dose escalation experiments revealed that either too large volume or too many virus particles caused inflammation and necrosis in the target tissue, whereas 109 plaque forming units injected in multiple aliquots resulted in transgene expression with only mild immune reactions.
Conclusions
We show the first evidence of biologically significant baculoviral gene transfer in skeletal muscle of NZW rabbits using VEGF‐DΔNΔC as a therapeutic transgene. Copyright © 2012 John Wiley & Sons, Ltd. |
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AbstractList | Background
Occluded arteries and ischemic tissues cannot always be treated by angioplasty, stenting or by‐pass‐surgery. Under such circumstances, viral gene therapy may be useful in inducing increased blood supply to ischemic area. There is evidence of improved blood flow in ischemic skeletal muscle and myocardium in both animal and human studies using adenoviral vascular endothelial growth factor (VEGF) gene therapy. However, the expression is transient and repeated gene transfers with the same vector are inefficient due to immune responses.
Methods
Different baculoviral vectors pseudotyped with or without vesicular stomatitis virus glycoprotein (VSV‐G) and/or carrying woodchuck hepatitis virus post‐transcriptional regulatory element (Wpre) were tested both in vitro and in vivo. VEGF‐DΔNΔC was used as therapeutic transgene and lacZ as a control. In vivo efficacy was evaluated as capillary enlargement and transgene expression in New Zealand White (NZW) rabbit skeletal muscle.
Results
A statistically significant capillary enlargement was detected 6 days after gene transfer in transduced areas compared to the control gene transfers with baculovirus and adenovirus encoding β‐galactosidase (lacZ). Substantially improved gene transfer efficiency was achieved with a modified baculovirus pseudotyped with VSV‐G and carrying Wpre. Dose escalation experiments revealed that either too large volume or too many virus particles caused inflammation and necrosis in the target tissue, whereas 109 plaque forming units injected in multiple aliquots resulted in transgene expression with only mild immune reactions.
Conclusions
We show the first evidence of biologically significant baculoviral gene transfer in skeletal muscle of NZW rabbits using VEGF‐DΔNΔC as a therapeutic transgene. Copyright © 2012 John Wiley & Sons, Ltd. Abstract Background Occluded arteries and ischemic tissues cannot always be treated by angioplasty, stenting or by‐pass‐surgery. Under such circumstances, viral gene therapy may be useful in inducing increased blood supply to ischemic area. There is evidence of improved blood flow in ischemic skeletal muscle and myocardium in both animal and human studies using adenoviral vascular endothelial growth factor (VEGF) gene therapy. However, the expression is transient and repeated gene transfers with the same vector are inefficient due to immune responses. Methods Different baculoviral vectors pseudotyped with or without vesicular stomatitis virus glycoprotein (VSV‐G) and/or carrying woodchuck hepatitis virus post‐transcriptional regulatory element (Wpre) were tested both in vitro and in vivo . VEGF‐D ΔNΔC was used as therapeutic transgene and lacZ as a control. In vivo efficacy was evaluated as capillary enlargement and transgene expression in New Zealand White (NZW) rabbit skeletal muscle. Results A statistically significant capillary enlargement was detected 6 days after gene transfer in transduced areas compared to the control gene transfers with baculovirus and adenovirus encoding β‐galactosidase ( lacZ ). Substantially improved gene transfer efficiency was achieved with a modified baculovirus pseudotyped with VSV‐G and carrying Wpre. Dose escalation experiments revealed that either too large volume or too many virus particles caused inflammation and necrosis in the target tissue, whereas 10 9 plaque forming units injected in multiple aliquots resulted in transgene expression with only mild immune reactions. Conclusions We show the first evidence of biologically significant baculoviral gene transfer in skeletal muscle of NZW rabbits using VEGF‐D ΔNΔC as a therapeutic transgene. Copyright © 2012 John Wiley & Sons, Ltd. |
Author | Nieminen, Tiina Lesch, Hanna P. Airenne, Kari J. Kaikkonen, Minna U. Roschier, Miia M. Karvinen, Henna Laitinen, Olli H. Heikura, Tommi Rissanen, Tuomas T. Mähönen, Anssi J. Ylä-Herttuala, Seppo |
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CitedBy_id | crossref_primary_10_3390_v10100574 crossref_primary_10_1016_j_addr_2014_01_004 crossref_primary_10_3390_v12010078 crossref_primary_10_1182_blood_2013_04_495432 crossref_primary_10_1016_j_plasmid_2018_05_002 crossref_primary_10_3390_v7042099 crossref_primary_10_1016_j_jbiotec_2016_05_007 crossref_primary_10_1016_j_jviromet_2018_02_001 crossref_primary_10_1038_ncomms11529 crossref_primary_10_1016_j_addr_2019_06_002 crossref_primary_10_1038_mt_2012_286 crossref_primary_10_1002_jgm_2756 crossref_primary_10_3390_biom8010001 |
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Occluded arteries and ischemic tissues cannot always be treated by angioplasty, stenting or by‐pass‐surgery. Under such circumstances, viral gene... Abstract Background Occluded arteries and ischemic tissues cannot always be treated by angioplasty, stenting or by‐pass‐surgery. Under such circumstances,... |
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SubjectTerms | angiogenesis baculovirus gene therapy vascular endothelial growth factor |
Title | Baculovirus-mediated vascular endothelial growth factor-DΔNΔC gene transfer induces angiogenesis in rabbit skeletal muscle |
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