Table 1.
Suitability of animal models of HBV infection for evaluating oligonucleotide-based therapies.
| Model | SVP Production | Genetic Diversity (Pre-Existing ASO/Sirna Escape Mutants) |
Rapid Turnover of cccDNA (Evolution of ASO/RNAi Escape Mutants) |
TLR9 Activity (CpG DNA) |
TLR3 Reactivity (dsRNA/RNAi) |
|---|---|---|---|---|---|
| Human | LDL-based (SVP are spherical) |
Present | Present | Present (KCs) |
Present (LSECs, KCs) |
| Transgenic mice | LDL metabolism opposite to humans (SVP are octahedral) |
None | Present but turnover unknown | Yes but human and rodent CpG sequences differ | Stronger vs. primate |
| AAV/HDI-mice | LDL metabolism opposite to humans (SVP are octahedral) |
None | Present but turnover unknown | Yes but human and rodent CpG sequences differ | Stronger vs. primate |
| Scid-Hu mice | SVP production is attenuated (altered lipid metabolism) |
Present (limited due to short term infection) |
Yes | Yes but human and rodent CpG sequences differ | Stronger vs. primate |
| Ducks | LDL metabolism similar to humans | Present (limited due to short term infection) |
Yes | Yes but via altered reactivity by TLR15 | Similar to primate |
| Woodchucks | LDL metabolism opposite to humans | Present (chronic infection) |
Yes | Yes but human and rodent CpG sequences differ | Similar to primate |