| Adeno virus |
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1)
Transfect a wide variety of cell types in the inner ear including spiral ganglions, outer hair cells, spiral ligament, stria vascularis, and mesenchymal cells in both auditory and vestibular systems.
-
2)
Can produce high titer values that allow injection of small dose volumes for gene therap.
-
3)
Transgene expression up to 3 weeks can be achieved. The short duration of gene expression is ideal for hair cell regeneration because prolonged Math1 expression can produce too many ectopic hair cellsand compromise hearing.
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4)
Effective in delivering Math1 gene to regenerate hair cells and Bcl-2 to protect hair cells from damage.
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5)
Allows insertion of large DNA segments. Recombinant forms can take up to 30kb foreign DNA.
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6)
Infects dividing and non-dividing cells with very high transduction efficiencies, both in vitro and in vivo.
-
7)
Widely researched in clinical studies in both animals and humans, giving a better ability to tackle clinical complications that can arise.
|
-
1)
Evokes a strong host immune response.
-
2)
Does not offer long term gene expression.
-
3)
Entry of the viral vectors is largely dependent on a host receptor called the coxsackie virus receptor (CAR).
|
[49,51, 82,83,84,87,88] |
| Adeno-associated Virus |
-
1)
Effectively transfect most inner ear cell types in vivo. Studies show transgene expression in cochlear blood vessels, nerve fibers and spiral limbus cells.
-
2)
Effective in targeting stria vascularis and delivering tropic factors like NT-3, BDNF, VEGF and FGF.
-
3)
Transgene expression can occur up to 24 weeks in vivo.
-
4)
Non-toxic to inner ear cells and evokes low immune response.5) Lacks pathogenicity and has never been associated with any known human disease making them suitable for clinical applications.
|
-
1)
Only effective with in vivo inner ear gene therapy.
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2)
Successful transgene expression in vivo depends on route of vector administration, limited to only direct injection of vector.
-
3)
Previous studies haveshown possible dissemination of vector from target tissue.
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4)
Offers only a limited payload capacity owing to its small size.
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5)
Risk of insertional mutagenesis.
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6)
No substantial clinical experience.
-
7)
Vector entry in to host largely depends on heparin sulfate receptor.
|
[76,89,90,91,92] |
| Herpes Simplex Virus |
-
1)
Effectively known to target non-dividing cells, specific to nerve cells, spiral ganglion, vestibular ganglion and mesenchymal cells in mice and guinea pigs.
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2)
Newer recombinant vectors offer stable and long term gene expression of up to 8 weeks.
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3)
Can take large DNA fragments.
|
-
1)
Evokes a strong immune response.
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2)
Transfection is limited only to non-dividing neuronal cells.
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3)
Large size of the virusmakes it difficult tomanipulate.
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4)
The virus does not integrate into the host genome; hence gene expression can be unstable.
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5)
Difficult to produce high titer values and requires injection of high vector volumes.
-
6)
No substantial clinical experience.
|
[84,85,93] |
| Lentivirus |
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1)
Transfect both dividing and non-dividing cells, including stem cells that are very difficult to transfect.
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2)
Effectively transduce spiral ganglion neurons and supporting cell in vitro.
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3)
Studies indicate transgene expression in perilymphatic space for up to 2 weeks.
|
-
1)
Limited to use in production of genes only in the perilymph.
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2)
Limited dissemination of vector and not suitable for sensory cell transduction.
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3)
Failure to transduce cells in the sensory epithelium in vivo.
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4)
Can randomly integrate into host chromosome and capable of generating a replication competent virus.
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5)
No clinical experience and safety concern arise from human immune deficiency virus origin.
|
[86,94] |
