Table 2.
Summary of gene therapy strategies for radioprotection.
| Gene, Mechanism of Action |
Vector | Administration | Effects | Ref. |
|---|---|---|---|---|
| Superoxide Dismutase (SOD2, MnSOD), radioprotector |
Adenovirus | Intratracheal Injection |
Decreased alveolitis and expression of IL- 1, TNF-α, and TGF-β |
12,14 |
| Herpes Simplex Virus 1 |
Intestinal Injection |
Preservation of villi area | 13 | |
| Plasmid/ Liposome |
Intratracheal Injection |
Decreased expression of IL-1, TNF-α, TGF-β, VCAM-I and ICAM-I, increased survival, no protection of tumors |
19,26, 28 |
|
| Inhalation | Increased survival | 16 | ||
| Intravesicular Instillation |
Enhanced recovery of barrier function, improved voiding |
15 | ||
| Intraesophageal Injection |
Increased survival, decreased weight loss, tongue ulceration, xerostomia, lipid peroxidation, and recombination |
20,21, 24,31 |
||
| Intravenous Injection |
Increased survival | 34 | ||
| Minicircle Plasmid |
Intraesophageal Injection |
Increased survival | 18 | |
| Intravenous Injection |
Increased survival | 18 | ||
| Catalase, radioprotector |
Plasmid/ Liposome |
Intratracheal Injection |
Increased survival, decreased alveolitis | 35 |
| Retrovirus | Ex-vivo infection | Improved engraftment of hematopoietic stem cells |
36 | |
| Roof-plate specific spondin 1 (Rspondin1), radiomitigator |
Adenovirus | Intravenous Injection |
Increased survival, decreased weight loss, decreased crypt apoptosis |
45 |
| Heat Shock Protein 25 (HSP25), unclear (possible radioprotector or radiomitigator) |
Adenovirus | Salivary Gland Injection |
Increased salivary gland mass, increased salivary flow rate, reduction of acinar cell apoptosis, reduction of fibrosis |
47 |
| Intravenous Injection |
Enhanced bone marrow recovery, protection of hematopoietic stem cells |
48 | ||
| Multidrug Resistance 1 (MDR1), radiomitigator |
Retrovirus | In vitro Infection | Decreased expression of pro-apoptotic genes, increased cell survival |
60 |
| Lentiviral self- inactivating vector |
In vitro Infection | Increased cell survival | 61 | |
| Snail Family Zinc Finger 2 (SNAI2), radiomitigator |
Lentiviral self- inactivating vector |
In vitro Infection | Increased cell survival, apoptosis |
63 |
| Interleukin 3, radiomitigator |
Plasmid Conjugated with Antibody |
Intravenous Injection |
Expression of IL-3 in bone marrow and spleen |
67 |
| Hepatocyte Growth Factor (HGF), radiomitigator |
Adenovirus | Myocardial Injection |
Improved local perfusion, decreased fibrosis, improved ventricular function |
71 |
| Adenovirus | Intravenous Injection |
Increased RBC and WBC, increased cellularity of bone marrow, increased survival |
72 | |
| Fibroblast Growth Factor 2 (FGF2) and Vascular Endothelial Growth Factor (VEGF), radiomitgator |
Adenovirus | Retrograde Ductal Delivery to Salivary Glands |
Increased microvessel density, increased salivary flow |
77 |
| Keratinocyte Growth Factor (KGF), radiomitigator |
Adenovirus with retroviral elements (ref. 81) |
Retrograde Ductal Delivery to Salivary Glands |
Reduced oral ulceration, improved weight gain, improved salivary flow, no effect on tumor growth |
85, 86 |
| Erythropoietin (Epo), radiomitigator |
Adenovirus with retroviral elements (ref. 81) |
Retrograde Ductal Delivery to Salivary Glands |
Increased tear production, corneal epithelium preservation, increased VEGF receptor expression |
91 |
| Aquaporin-1 (AQP1), restoration of tissue function |
Adenovirus | Retrograde Ductal Delivery to Salivary Glands |
Increased salivary gland output in animal and human trials |
94-97 |
| Adeno- Associated Virus |
Retrograde Ductal Delivery to Salivary Glands |
Increased salivary gland output | 98 |