rAd |
|
|
|
|
|
|
|
First generation r-Ad
|
E1a, E1b, E3 |
neurons, glia |
episomal |
~8kb |
High Antigenicity |
high protein production variable durability pending promoter and immune response |
High Toxicity |
Gutless “high capacity”
|
All structural genes |
neurons, glia |
episomal |
<37kb |
|
variable protein production long-term |
Toxicity dependent on titer |
rAAV |
|
|
|
|
|
|
|
rAAV1–10 |
rep, cap
|
neurons |
episomal/integrated |
~4.7kb |
Potential antigenicity due to capsid proteins |
high protein production long-term |
Insertional Mutagenesis?/immune response |
rHSV |
|
|
|
|
|
|
|
replication-defective |
ICP4, ICP22, ICP27, ICP47 |
neurons, glia |
episomal/latent |
~20kb |
Moderate Antigenicity |
high protein production short term |
Moderate Toxicity |
Am plicon |
|
|
|
|
|
|
|
|
All except oris and pac
|
neurons, glia |
episomal/latent |
~20kb |
Low Antigenicity |
low protein production short-term |
Low Toxicity |
rLV |
|
|
|
|
|
|
|
1st generation rLV
|
vif, vpr, vpu, nef |
neurons*
|
integrated |
~9kb |
low |
high protein production long term |
potential problems from VSV-g, pseudotyped envelope, possible HIV sero-conversion, possible recombination |
2st generation rLV
|
vif, vpr, vpu, nef |
neurons*
|
integrated |
~9kb |
low |
high protein production long term |
potential problems from VSV-g, pseudotyped envelope, possible HIV sero-conversion, possible recombination |
3rd generation rLV
|
vif, vpr, vpu, nef tat, rev |
neurons*
|
integrated |
~9kb |
Moderate Antigenicity |
high protein production long term |
VSV-g, seroconversion, recombination |
Self-Inactivating |
All above and 5′ LTR inactivation |
neurons*
|
integrated |
~9kb |
Low Antigenicity |
high protein production long term |
VSV-g, seroconversion |