| Technologies for HSCT Gene Therapy |
Advantages |
Disadvantages |
| g-Retroviral Vectors |
•Ability to target many cell types
•Long-term expression due to integration
•Increased safety due to SIN development |
•Requirement for cellular division
•Necessity of cytokine cocktails to stimulate HSC cycling
•Insertional mutagenesis potential
•Complex manufacturing |
| Lentiviral Vectors |
•Wide range of cell targets
•Long term expression due to integration
•HIV-based human cell specificity
|
•Require multiple plasmids/elements provided in trans for production
•Risk of insertional mutagenesis
•Complex manufacturing |
|
Sleeping Beauty Transposon Systems (SBTS) |
•Low complexity
•Simple manufacturing (plasmid DNA only)
•Potentially reduced immunogenic response
|
•Lower-level expression of the transgene product
•Random insertion pattern
•Potential for secondary or tertiary transposition events |
| Zinc Finger Nucleases (ZFNs) |
•Targeted gene correction or addition
•Potential to utilize endogenous genetic control elements
•Long-term expression through chromosomal integration |
•Safety remains undetermined
•Risk of off-target mutagenesis
•Require additional means of cellular entry
•Limited sequence targeting potential
|
| Peptide Nucleic Acids (PNAs) |
•Site-specific modification
•Useful in gene silencing
•In vivo delivery and functionality possible |
•Limited research to date
•Risk of off-target sitesof genetic modification
•Low efficiency |
