Review Article

Effects of HBV Genetic Variability on RNAi Strategies

Table 1

Successful RNAi strategies targeting HBV utilising genomic conservation.

GroupDesign of the RNAi effectorRNAi approachExperimental systemNucleotide position*Designated nameTarget sequenceRNAi effect (% reduction)Ref.

416–434Sh6CTGCTATGCCTCATCTTCT95% (encapsidated pgRNA), 98% (DNA)
458–4761740 SLASGGTATGTTGCCCGTTTGTC92% (encapsidated pgRNA), 96% (DNA)
720–738Sh10CTGTTTGGCTTTCAGTTAT95% (encapsidated pgRNA), 98% (DNA) [7]
1823–1841DR1TTTCACCTCTGCCTAATCA96% (DNA)
1848–1867Eps32TTCATGTCCCTACTGTTCAA96% (DNA)
ISequence conservation among HBV genotypesshRNA expression vector (Pol II/III promoter)Liposome delivery/human liver cell line2421–2439Sh1GTCGCAGAAGATCTCAATC86% (encapsidated pgRNA), 96% (DNA)
458–476S1GGTATGTTGCCCGTTTGTC90% (total RNA, DNA)[10]
1317–1337PRE1317AAAGCTCATCGGAACTGACAA80% (cccDNA)[14]
245–265B245AGTCTAGACTCGTGGTGGACT~80% (pgRNA, pcRNA), 90% (DNA)
376–396B376GATGTGTCTGCGGCGTTTTAT~80% (pgRNA, pcRNA, DNA) [13]
1581–1601B1581GCACTTCGCTTCACCTCTGCA~70% (pgRNA, pcRNA), 80% (DNA)
1778–1798 (sic)B1789AGGCTGTAGGCATAAATTGGT~70% (pgRNA, pcRNA) 80% (DNA)

IISequence conservation among HBV genotypesmiRNA expression vector (Pol II promoter)Liposome delivery/human liver cell line761–782Mir-155-S608CCAAGTCTGTACAGCATCGTGA80% (HBs mRNA)[52]
1575–1599Mir-51/5
Mir-122/5
CCGTGTGCACTTCGCTTCACCTCTG90% (HBsAg)[24]

IIIAnalysis of a single genotype (representative examples)shRNA expression vectors (Pol III promoter)Viral vectors/human liver cell line456–476S1AAGGTATGTTGCCCGTTTGTC90% (Total RNAs) [40]
1644–1664X1AAGGTCTTACATAAGAGGACT90% (Total RNAs)
322–342S1AACCTCCAATCACTCACCAAC80% (HBsAg)
540–560S2AAGGAACCTCTATGTATCCCT80% (HBsAg)[53]
589–609S3AAATTGCACCTGTATTCCCAT80% (HBsAg)

*indicates EcoRI site-based numbering systems using Genotype A (AM282986) as described in [6].