Table 1.
Examples of viral vectors used for gene therapy applications.
| Virus | Genome | Insert Size | Advantages and Limitations |
|---|---|---|---|
| Adenovirus | |||
| Ad5 | dsDNA | <7.5 kb | Broad host range (dividing and non-dividing cells) [13] |
| Ad26 | Excellent packaging capacity of HC-Adv [17] | ||
| ChAd | Persistent expression, no chromosomal integration [20] | ||
| HC-AdV | 37 kb | Strong immunogenicity [14], reduced for gutless Ad [16] | |
| Oncolytic Ad vectors for tumor targeting and killing [18] | |||
| Pre-existing immunity in humans [13] | |||
| Packaging cell lines for large-scale GMP production [19] | |||
| AAV | |||
| AAV2, 3 | ssDNA | 4 kb | Relatively broad host range [22] |
| AAV5, 6 | Limited packaging capacity [22] improved by Dual AAV vectors [23,24] | ||
| AAV8, 9 | Strong immune response after AAV re-administration, which could be reduced by re-administration with different AAV serotypes [25] | ||
| Dual AAV | Exo-AAV vectors have reduced immunogenicity, providing liver-targeted transgene expression [26,27] | ||
| Exo-AAV | Generally, AAV remains in an extrachromosomal state [28] | ||
| HSV | |||
| HSV-1 | dsDNA | >30 kb | Broad host cell range [31], excellent [33], extreme for HSV amplicons [34] foreign DNA packaging capacity |
| HSV-2 | Long-lasting transgene expression from extrachromosomal circular HSV DNA [32] | ||
| HSV amplicons | 150 kb | Deletion of non-essential HSV genome reduces cytotoxicity [35] | |
| Engineering of oncolytic HSV by introduction of miR145 [36] | |||
| Engineering of helper virus-free packaging system [37] | |||
| γ -Retrovirus | |||
| MMSV | ssRNA | 8 kb | Restricted host range, only dividing cells [38] |
| MSCV | Good packaging capacity of foreign genetic material [38] | ||
| SIN-γRV | Chromosomal integration due to reverse transcriptase activity [39] | ||
| Random integration causing leukemia [8] | |||
| Targeted integration with self-inactivating vector [40] | |||
| Packaging cell lines for large-scale production [44] | |||
| Lentivirus | |||
| HIV-1 | ssRNA | 8kb | Broad host range, including non-dividing cells [45] |
| HIV-2 | Good capacity to accommodate foreign genetic material [45] | ||
| SIV | Non-random chromosomal integration [46] | ||
| FIV | Non-human LV vectors available [47,48,49,50] | ||
| EIAV | Producer cell lines engineered for LV vectors [51] | ||
| Alphavirus | |||
| SFV, SIN, | ssRNA | 8 kb | Extremely broad host range, risk of neurovirulence [52] |
| VEE, M1 | Good packaging capacity [53] | ||
| RNA self-replication leading to extreme transgene expression [52] | |||
| Low immunogenicity of alphaviruses [52] | |||
| Transient expression not applicable for chronic diseases, but good for acute diseases and vaccines [52] | |||
| Flexibility to use viral particles, RNA and DNA replicons for delivery [54] | |||
| Oncolytic alphaviruses for cancer therapy [58,59] | |||
| Flavivirus | |||
| KUN, WNV, | ssRNA | 6 kb | Broad host range, relatively good packaging capacity [60] |
| DENV, TBEV | RNA self-replication leading to high transgene expression [60] | ||
| YFV, ZIKV | Flexibility to use viral particles, RNA and DNA replicons for delivery [60] | ||
| Efficient packaging cell lines for KUN [66] and TBEV [63] | |||
| Measles virus | |||
| MV | ssRNA | 6 kb | Broad host range, relatively good packaging capacity [67] |
| Positive strand RNA template needed for translation [68] | |||
| Development of reverse genetics [69] and packaging cell lines [70] | |||
| Oncolytic MV strains for cancer therapy [71,72] | |||
| Rhabdovirus | |||
| VSV | ssRNA | 6 kb | Broad host range, relatively good packaging capacity [73] |
| RABV | Positive strand RNA template needed for translation [73] | ||
| Maraba | Reverse genetics systems [74] | ||
| Oncolytic rhabdoviruses for cancer therapy [75,76] | |||
| Vaccinia-free packaging cell lines [77] | |||
| NDV | |||
| NDV | ssRNA | 4 kb | Broad host range, modest packaging capacity [78] |
| Reverse genetics systems available [79] | |||
| Oncolytic NDV for killing of tumor cells [79] | |||
| Poxvirus | dsDNA | >30 kb | |
| VV | Broad host range [80] | ||
| Avipox | Excellent packaging capacity [80] | ||
| Tumor-selective replication-competent VV [81] | |||
| Picornavirus | |||
| CVA21 | ssRNA | 6 kb | Relatively broad host range [82] |
| CVB3 | Relatively good packacking capacity despite the small size [82] | ||
| PV-1 | No chromosomal integration [82] | ||
| Applications for gene therapy and vaccines [83,84] | |||
| Reovirus | |||
| Reovirus-3 | dsRNA | ND | Oncolytic activity in different types of cancer cells [85] |
| Reoviruses replicate preferentially in Ras activated tumor cells [86] | |||
| Combination therapy with radio-, chemo-, and immunotherapy [87] | |||
| Endoplasmic reticular stress-mediated apoptosis in cancer cells [88] | |||
| Polyoma virus | |||
| SV40 | dsDNA | 17.7 kb | Superb packaging capacity of 17.7 kb for SV40 with small genome [89] |
| Vero cell-based SV40 packaging system [90] | |||
| Inhibition of tumor cell progression [91] |
AAV, adeno-associated virus; Ad, adenovirus; CVA21, coxsackievirus A21; CVB3, coxsackievirus B3; DENV, Dengue virus; dsDNA, double-stranded DNA; dsRNA, double-stranded RNA; Exo-AAV, exosome-associated AAV; FIV, feline immunodeficiency virus; HC-Adv, high-capacity Ad gutless vector; HIV, human immunodeficiency virus; HSV, herpes simplex virus; KUN, Kunjin virus; M1, oncolytic alphavirus; MMSV, Moloney murine sarcoma virus; MSCV, murine stem cell virus; ND, not determined; NDV. Newcastle disease virus; PV-I, poliovirus-1; SFV, Semliki Forest virus; SIN, Sindbis virus; SINγRV, self-inactivating gamma retrovirus; SIV, simian immunodeficiency virus; ssDNA, single-stranded DNA; ssRNA, single-stranded RNA; TBEV, tick-borne encephalitis virus; VEE, Venezuelan equine encephalitis virus; VV, vaccinia virus; WNV, West Nile virus; YFV, yellow fever virus; ZIKV, Zika virus.