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Virus | Genome | Capacity | Features |
---|---|---|---|
Ad | dsDNA | 7.5-37 kb | Extrachromosomal, short- and long-term expression [14] |
AAV HSV RV LV Alphavirus Flavivirus Paramyxovirus Rhabdovirus NDV Poxvirus Picornavirus Reovirus Polyomavirus |
ssDNA dsDNA ssRNA ssRNA ssRNA ssRNA ssRNA ssRNA ssRNA dsDNA ssRNA dsRNA dsDNA |
4 kb 30-150 kb 8 kb 8 kb 8 kb 6 kb 6 kb 6 kb 4 kb > 30 kb 6 kb ND 17.7 kb |
Extrachromosomal, integration for long-term expression [10] Extrachromosomal, long-term expression, latency [11] Integration, long-term expression [12] Integration, long-term expression, transduction of non-dividing cells [13] Extreme short-term expression, RNA degradation [18] Extreme short-term expression, RNA degradation [19] Short-term expression, RNA degradation [20] Short-term expression, RNA degradation [21] Short-term expression, oncolytic activity [22] Extrachromosomal expression [23] Extrachromosomal expression [24,25] Extrachromosomal expression [24] Extrachromosomal expression [23] |
Cancer | Vector | Target | Findings |
---|---|---|---|
Esophageal | Ad | p53 | Significant tumor suppression of tumor growth in nude mice [50] |
Ovarian HNSCC Head & neck Melanoma Melanoma Melanoma HGG HGG HGG Sarcoma Solid tumors Melanoma Glioma Breast Prostate Ovarian Prostate Prostate |
Ad Ad Ad HSV T-VEC HSV T-VEC HSV T-VEC RRV Toca 511 RRV Toca 511 RRV Toca 511 Reovirus Reovirus Reovirus Reovirus Reovirus MV MV VEE VEE |
p53 p53 p53 GM-CSF GM-CSF GM-CSF yCD yCD yCD Reolysin Reolysin Reolysin Reolysin Reolysin CEA CEA PSMA PSMA |
Prolonged survival in mice with implanted tumors [51] Safe and promising results in clinical trials [52] Approved as GendicineTM for head & neck cancer in China [53] Enhanced tumor growth inhibition, prolonged survival in mice [55] Minor adverse events, good therapeutic efficacy in Phase II and III [56] Approval for melanoma treatment in the US, Europa, and Australia [57] Extended survival in mice with orthotopic gliomas [58] Prolonged survival of 13.6 months in HGG patients in phase I [59] No overall extension of survival in HGG patients in phase II/III [60] Inhibition of tumor growth in nude mice [61] Clinical benefits in phase I: 1 PR, 7 SD [62] Good safety and clinical efficacy in melanoma patients in phase II [63] Orphan drug designation for malignant glioma [64] Fast Track designation for metastatic breast cancer [65] Delayed tumor growth, prolonged survival in mice [66] SD in all 9 patients, prolonged OS survival of 12.15 months in phase I [67] Robust PSMA-specific immune responses in mice [68] Good safety, and tolerability, but weak immunogenicity in phase I [69] |
Disease | Vector | Target | Findings |
---|---|---|---|
Heart failure | Ad | SERCa2a | Restored systolic & diastolic heart functions rat heart model [71] |
Heart failure Heart failure Heart failure Heart failure Heart failure DMT1 AAT AAT |
AAV1 LV AAV1 AAV1 AAV1 AAV2 AAV2 AAV2 |
SERCa2a SERCa2a SERCa2a SERCa2a SERCa2a hAAT hAAT hAAT |
Enhanced coronary blood flow in pig heart failure model [72] Improved systolic & diastolic functions, reduced mortality in rats [73] Improved functional, symptomatic and ventricular activity in phase I [74] Improved walking, peak oxygen consumption in phase II [75] Reduced cardiovascular events and deaths in Phase II [76] Reduced insulitis, insulin autoantibodies, and DTM1 in mice [77] Sustained AAT expression > 1 year in AAT patients in phase I [78] Immunostaining of AAT in AAT patients in phase II [79] |
Disease | Vector | Target | Findings |
---|---|---|---|
Hemophilia A | Ad | FVIII | Expression of physiological levels of FVIII in mice [83] |
Hemophilia A Hemophilia A Hemophilia A Hemophilia A Hemophilia A Hemophilia A Hemophilia A Hemophilia B Hemophilia B Hemophilia B Hemophilia B Hemophilia B Hemophilia B Hemophilia B Hemophilia B Hemophilia B β-thalassemia β-thalassemia β-thalassemia β-thalassemia SCD SCD SCD |
AAV6/AAV8 AAV8 AAV8/AAV9 LV-BM AAV AAV5 AAV5 Ad Ad Ad +CsA AAV8 AAV8 scAAV2 scAAV2 AAVS3 SIN-LV LentiGlobin LentiGlobin GLOBE LV GLOBE LV LV-HSC LentiGlobin LentiGlobin |
FVIII FVIII FVIII FVIII FVIII FVIII-SQ FVIII FIX cFIX cFIX FIX FIX FIX FIX FIX FIX HbAT87Q HbAT87Q Mini-β Mini-β βA globin HbAT87Q HbAT87Q |
Therapeutic FVIII levels lasting for > 3 years in dogs [87] 1-2% of normal FVIII levels, 90% reduction of bleeding in dogs [88] 1.9-11.3% of normal FVIII levels in dogs [89] Sustained FVIII activity, hemophilia A phenotype correction in mice [90] 8-60% of normal FVIII levels in hemophilia A patients in phase II [91] Clinical benefits: less bleeding, no need for prophylactic FVIII [92] Conditional EMA marketing approval for severe hemophilia A [93] Expression of FIX for > 300 days in mice [94] Complete correction of hemophilia B phenotype in dogs [95] Restored therapeutic FIX for 6 months with CsA in dogs [96] 25-200% FIX activity, correction of hemophilic phenotype in dogs [97] 1-6% of normal FIX, reduced bleeding episodes in patients in phase I [98] Correction of coagulation function in FIX-deficient mice [100] Significant reduction of bleeding episodes in hemophilia B patients [91] FIX expression for 27 months in hemophilia B patients in phase I/II [102] Stable long-term FIX expression in dogs [103] Blood transfusions terminated in β-thalassemia patients in phase I [104] Independence of transfusions in β-thalassemia patients in phase III [105] Normalized phenotype after in utero gene therapy [106] Reduced or no need for transfusion in β-thalassemia patients [107] Anti-sickling protein expression for 10 months in mice [108] Case report of complete remission of SCD patient [109] Complete resolution of vaso-occlusive events in SCD patients [110] |
Disease | Vector | Target | Findings |
---|---|---|---|
PD PD PD PD PD PD PD PD PD PD PD PD HD HD HD SMA SMA SMA SMA |
AAV AAV AAV LV AAV LV LV AAV AAV AAV LV LV AAV5 AAV5 AAV5 AAV8 AAV8 AAV8 AAV9 |
GAD65 GAD GDNF GDNF GDNF GDNF GDNF hAADC hAADC TH, GCH, hAADC ProSavin ProSavin miHTT miHTT miHTT hSMN hSMN hSMN hSMN1 |
Reduced PD symptoms and relief of pain in rat models [113] Safe, improved motor neuron functions in PD patients in phase I [114] Regeneration, functional activity in 6-OHDA-lesioned rats [115] Regeneration, functional activity in 6-OHDA-lesioned rats [115] Regeneration, functional activity in MTTP-lesioned primates [115] Regeneration, functional activity in MTTP-lesioned primates [115] Reversed functional and motor deficits in macaques [116] 50% improvement in L-Dopa responsiveness in primates [117]. Significant improvement in PD patients for 2 years [118] Enhanced BH4 and dopamine production, improved rotational behavior in rats [119] Significant motor function improvement in PD patients [120] Long-term (4 years) motor function improvement in PD patients [121] Prevention of mutant HTT, decrease in neuronal dysfunction in rats [122] Reduced HTT mRNA and protein levels in transgenic minipigs [123] Good safety and tolerability in HD patients in phase I/II [124] Improved muscle strength, coordination and locomotion in mice [125] Improved motor function and prolonged survival in SMA patients [126] Improved motor function and prolonged survival in SMA patients [127] Approval for SMA patients in the US, the EU and Canada [128] |
Disease | Vector | Target | Findings | |
---|---|---|---|---|
Muscular | ||||
Dystrophy | AAV6 | µDys | Restored Dys expression, reduced muscle pathology in mice [131] | |
Dystrophy | AAV6 | µDys | Efficient Dys distribution in skeletal muscles in a canine model [132] | |
DMD | rAAVrh74 | µDys | Therapeutic Dys levels, improved NSAA scores in 4 DMD patients [133] | |
DMD | AAV9 | mini-Dys | Phase I in progress in 4-12-year-old DMD patients [134] | |
Immunodeficiency | ||||
SCID-X1 | γRV | IL2RG | SCID-X1 correction in pediatric patients [136], few leukemia cases [137] | |
SCID-X1 | γRV | IL2RG | Long-term clinical benefits in 8 out of 10 patients [136] | |
SCID-X1 | γRV | IL2RG | Normal growth, and protection against infections after 18 years [138] | |
SCID-X1 | γRV | IL2RG | Unfavroable chromosomal integration causing T-ALL [139] | |
SCID-X1 | SIN-γRV | IL2RG | No cases of leukemia in 9 treated SCID-X1 patients [141] | |
SCID-X1 | SIN-LV | IL2RG | No cases of leukemia in 44 treated SCID-X1 patients [141] | |
ALD | SIN-LV | ABCD1 | Prevention of cerebral demyelination, clinical benefits [140] | |
ALD | SIN-γRV | ADA | Metabolic correction, high OS in ADA-SCID patients [142] | |
ADA-SCID | SIN-LV | ADA | Metabolic correction, high OS in ADA-SCID patients [143] |
Disease | Vector | Target | Findings |
---|---|---|---|
COVID-19 | ChAdOx1 nCoV-19 | SARS-CoV-2 S | Good safety and 62-90% efficacy in Phase III [144] |
COVID-19 COVID-19 COVID-19 COVID-19 COVID-19 COVID-19 COVID-19 EVD EVD EVD |
Ad5-S-nb2 rAd26-S/rAd5-S Ad26.COV2.S ChAdOx1 nCoV-19 Ad5-S-nb2 rAd26-S/rAd5-S Ad26.COV2.S VSV-ZEBOV VSV-ZEBOV VSV.ZEBOV |
SARS-CoV-2 S SARS-CoV-2 S SARS-CoV-2 S SARS-CoV-2 SARS-CoV-2 SARS-CoV-2 SARS-CoV-2 EBOV GP EBOV GP EBOV GP |
Good safety and efficacy in Phase III [145] Good safety and efficacy in Phase III [146] Good vaccine efficacy after a single dose [147] EUA in the UK in December 2020 [148] EUA in China in February 2021 [148] Approval in Russia in August 2020 [149] EUA in the US in February 2021 [148] Good safety and efficacy in Phase III [150] Good safety and efficacy in Phase III [151] Approval for EVD in 2020 [152] |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
Submitted:
20 April 2023
Posted:
21 April 2023
You are already at the latest version
This version is not peer-reviewed
Submitted:
20 April 2023
Posted:
21 April 2023
You are already at the latest version
Virus | Genome | Capacity | Features |
---|---|---|---|
Ad | dsDNA | 7.5-37 kb | Extrachromosomal, short- and long-term expression [14] |
AAV HSV RV LV Alphavirus Flavivirus Paramyxovirus Rhabdovirus NDV Poxvirus Picornavirus Reovirus Polyomavirus |
ssDNA dsDNA ssRNA ssRNA ssRNA ssRNA ssRNA ssRNA ssRNA dsDNA ssRNA dsRNA dsDNA |
4 kb 30-150 kb 8 kb 8 kb 8 kb 6 kb 6 kb 6 kb 4 kb > 30 kb 6 kb ND 17.7 kb |
Extrachromosomal, integration for long-term expression [10] Extrachromosomal, long-term expression, latency [11] Integration, long-term expression [12] Integration, long-term expression, transduction of non-dividing cells [13] Extreme short-term expression, RNA degradation [18] Extreme short-term expression, RNA degradation [19] Short-term expression, RNA degradation [20] Short-term expression, RNA degradation [21] Short-term expression, oncolytic activity [22] Extrachromosomal expression [23] Extrachromosomal expression [24,25] Extrachromosomal expression [24] Extrachromosomal expression [23] |
Cancer | Vector | Target | Findings |
---|---|---|---|
Esophageal | Ad | p53 | Significant tumor suppression of tumor growth in nude mice [50] |
Ovarian HNSCC Head & neck Melanoma Melanoma Melanoma HGG HGG HGG Sarcoma Solid tumors Melanoma Glioma Breast Prostate Ovarian Prostate Prostate |
Ad Ad Ad HSV T-VEC HSV T-VEC HSV T-VEC RRV Toca 511 RRV Toca 511 RRV Toca 511 Reovirus Reovirus Reovirus Reovirus Reovirus MV MV VEE VEE |
p53 p53 p53 GM-CSF GM-CSF GM-CSF yCD yCD yCD Reolysin Reolysin Reolysin Reolysin Reolysin CEA CEA PSMA PSMA |
Prolonged survival in mice with implanted tumors [51] Safe and promising results in clinical trials [52] Approved as GendicineTM for head & neck cancer in China [53] Enhanced tumor growth inhibition, prolonged survival in mice [55] Minor adverse events, good therapeutic efficacy in Phase II and III [56] Approval for melanoma treatment in the US, Europa, and Australia [57] Extended survival in mice with orthotopic gliomas [58] Prolonged survival of 13.6 months in HGG patients in phase I [59] No overall extension of survival in HGG patients in phase II/III [60] Inhibition of tumor growth in nude mice [61] Clinical benefits in phase I: 1 PR, 7 SD [62] Good safety and clinical efficacy in melanoma patients in phase II [63] Orphan drug designation for malignant glioma [64] Fast Track designation for metastatic breast cancer [65] Delayed tumor growth, prolonged survival in mice [66] SD in all 9 patients, prolonged OS survival of 12.15 months in phase I [67] Robust PSMA-specific immune responses in mice [68] Good safety, and tolerability, but weak immunogenicity in phase I [69] |
Disease | Vector | Target | Findings |
---|---|---|---|
Heart failure | Ad | SERCa2a | Restored systolic & diastolic heart functions rat heart model [71] |
Heart failure Heart failure Heart failure Heart failure Heart failure DMT1 AAT AAT |
AAV1 LV AAV1 AAV1 AAV1 AAV2 AAV2 AAV2 |
SERCa2a SERCa2a SERCa2a SERCa2a SERCa2a hAAT hAAT hAAT |
Enhanced coronary blood flow in pig heart failure model [72] Improved systolic & diastolic functions, reduced mortality in rats [73] Improved functional, symptomatic and ventricular activity in phase I [74] Improved walking, peak oxygen consumption in phase II [75] Reduced cardiovascular events and deaths in Phase II [76] Reduced insulitis, insulin autoantibodies, and DTM1 in mice [77] Sustained AAT expression > 1 year in AAT patients in phase I [78] Immunostaining of AAT in AAT patients in phase II [79] |
Disease | Vector | Target | Findings |
---|---|---|---|
Hemophilia A | Ad | FVIII | Expression of physiological levels of FVIII in mice [83] |
Hemophilia A Hemophilia A Hemophilia A Hemophilia A Hemophilia A Hemophilia A Hemophilia A Hemophilia B Hemophilia B Hemophilia B Hemophilia B Hemophilia B Hemophilia B Hemophilia B Hemophilia B Hemophilia B β-thalassemia β-thalassemia β-thalassemia β-thalassemia SCD SCD SCD |
AAV6/AAV8 AAV8 AAV8/AAV9 LV-BM AAV AAV5 AAV5 Ad Ad Ad +CsA AAV8 AAV8 scAAV2 scAAV2 AAVS3 SIN-LV LentiGlobin LentiGlobin GLOBE LV GLOBE LV LV-HSC LentiGlobin LentiGlobin |
FVIII FVIII FVIII FVIII FVIII FVIII-SQ FVIII FIX cFIX cFIX FIX FIX FIX FIX FIX FIX HbAT87Q HbAT87Q Mini-β Mini-β βA globin HbAT87Q HbAT87Q |
Therapeutic FVIII levels lasting for > 3 years in dogs [87] 1-2% of normal FVIII levels, 90% reduction of bleeding in dogs [88] 1.9-11.3% of normal FVIII levels in dogs [89] Sustained FVIII activity, hemophilia A phenotype correction in mice [90] 8-60% of normal FVIII levels in hemophilia A patients in phase II [91] Clinical benefits: less bleeding, no need for prophylactic FVIII [92] Conditional EMA marketing approval for severe hemophilia A [93] Expression of FIX for > 300 days in mice [94] Complete correction of hemophilia B phenotype in dogs [95] Restored therapeutic FIX for 6 months with CsA in dogs [96] 25-200% FIX activity, correction of hemophilic phenotype in dogs [97] 1-6% of normal FIX, reduced bleeding episodes in patients in phase I [98] Correction of coagulation function in FIX-deficient mice [100] Significant reduction of bleeding episodes in hemophilia B patients [91] FIX expression for 27 months in hemophilia B patients in phase I/II [102] Stable long-term FIX expression in dogs [103] Blood transfusions terminated in β-thalassemia patients in phase I [104] Independence of transfusions in β-thalassemia patients in phase III [105] Normalized phenotype after in utero gene therapy [106] Reduced or no need for transfusion in β-thalassemia patients [107] Anti-sickling protein expression for 10 months in mice [108] Case report of complete remission of SCD patient [109] Complete resolution of vaso-occlusive events in SCD patients [110] |
Disease | Vector | Target | Findings |
---|---|---|---|
PD PD PD PD PD PD PD PD PD PD PD PD HD HD HD SMA SMA SMA SMA |
AAV AAV AAV LV AAV LV LV AAV AAV AAV LV LV AAV5 AAV5 AAV5 AAV8 AAV8 AAV8 AAV9 |
GAD65 GAD GDNF GDNF GDNF GDNF GDNF hAADC hAADC TH, GCH, hAADC ProSavin ProSavin miHTT miHTT miHTT hSMN hSMN hSMN hSMN1 |
Reduced PD symptoms and relief of pain in rat models [113] Safe, improved motor neuron functions in PD patients in phase I [114] Regeneration, functional activity in 6-OHDA-lesioned rats [115] Regeneration, functional activity in 6-OHDA-lesioned rats [115] Regeneration, functional activity in MTTP-lesioned primates [115] Regeneration, functional activity in MTTP-lesioned primates [115] Reversed functional and motor deficits in macaques [116] 50% improvement in L-Dopa responsiveness in primates [117]. Significant improvement in PD patients for 2 years [118] Enhanced BH4 and dopamine production, improved rotational behavior in rats [119] Significant motor function improvement in PD patients [120] Long-term (4 years) motor function improvement in PD patients [121] Prevention of mutant HTT, decrease in neuronal dysfunction in rats [122] Reduced HTT mRNA and protein levels in transgenic minipigs [123] Good safety and tolerability in HD patients in phase I/II [124] Improved muscle strength, coordination and locomotion in mice [125] Improved motor function and prolonged survival in SMA patients [126] Improved motor function and prolonged survival in SMA patients [127] Approval for SMA patients in the US, the EU and Canada [128] |
Disease | Vector | Target | Findings | |
---|---|---|---|---|
Muscular | ||||
Dystrophy | AAV6 | µDys | Restored Dys expression, reduced muscle pathology in mice [131] | |
Dystrophy | AAV6 | µDys | Efficient Dys distribution in skeletal muscles in a canine model [132] | |
DMD | rAAVrh74 | µDys | Therapeutic Dys levels, improved NSAA scores in 4 DMD patients [133] | |
DMD | AAV9 | mini-Dys | Phase I in progress in 4-12-year-old DMD patients [134] | |
Immunodeficiency | ||||
SCID-X1 | γRV | IL2RG | SCID-X1 correction in pediatric patients [136], few leukemia cases [137] | |
SCID-X1 | γRV | IL2RG | Long-term clinical benefits in 8 out of 10 patients [136] | |
SCID-X1 | γRV | IL2RG | Normal growth, and protection against infections after 18 years [138] | |
SCID-X1 | γRV | IL2RG | Unfavroable chromosomal integration causing T-ALL [139] | |
SCID-X1 | SIN-γRV | IL2RG | No cases of leukemia in 9 treated SCID-X1 patients [141] | |
SCID-X1 | SIN-LV | IL2RG | No cases of leukemia in 44 treated SCID-X1 patients [141] | |
ALD | SIN-LV | ABCD1 | Prevention of cerebral demyelination, clinical benefits [140] | |
ALD | SIN-γRV | ADA | Metabolic correction, high OS in ADA-SCID patients [142] | |
ADA-SCID | SIN-LV | ADA | Metabolic correction, high OS in ADA-SCID patients [143] |
Disease | Vector | Target | Findings |
---|---|---|---|
COVID-19 | ChAdOx1 nCoV-19 | SARS-CoV-2 S | Good safety and 62-90% efficacy in Phase III [144] |
COVID-19 COVID-19 COVID-19 COVID-19 COVID-19 COVID-19 COVID-19 EVD EVD EVD |
Ad5-S-nb2 rAd26-S/rAd5-S Ad26.COV2.S ChAdOx1 nCoV-19 Ad5-S-nb2 rAd26-S/rAd5-S Ad26.COV2.S VSV-ZEBOV VSV-ZEBOV VSV.ZEBOV |
SARS-CoV-2 S SARS-CoV-2 S SARS-CoV-2 S SARS-CoV-2 SARS-CoV-2 SARS-CoV-2 SARS-CoV-2 EBOV GP EBOV GP EBOV GP |
Good safety and efficacy in Phase III [145] Good safety and efficacy in Phase III [146] Good vaccine efficacy after a single dose [147] EUA in the UK in December 2020 [148] EUA in China in February 2021 [148] Approval in Russia in August 2020 [149] EUA in the US in February 2021 [148] Good safety and efficacy in Phase III [150] Good safety and efficacy in Phase III [151] Approval for EVD in 2020 [152] |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
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