Figures & data
Figure 1 The RNAi mechanism is a powerful tool for gene silencing in mammalian cells. The siRNA pathway takes place as follows: (A) long dsRNA is cleaved by a member of RNAse III family, dicer, into around 21-nucleotide-long siRNAs. The siRNAs, generated either by (A) dicer cleavage or by (B) synthetic construction, are then introduced into cells, where they integrate into the RISC. Once unwound, the antisense strand of siRNA guides RISC to the mRNA containing its complementary sequence, which triggers the destruction of the target by the endonucleolytic cleavage. Springer Methods Mol Biol. RNAi-based functional pharmacogenomics. 2011;700:271–290, Tuzmen S, Tuzmen P, Arora S, Mousses S. Copyright 2011, with permission of Springer Nature.Citation1
Table 1 The selection of ongoing clinical trials of siRNA agents.
Figure 2 (A) Cytogenetic locus of TTR gene. (B) The human TTR gene. Reprinted by permission from Macmillan Publishers Ltd: Lab Invest. Teng MH, Yin JY, Vidal R, et al. Amyloid and nonfibrillar deposits in mice transgenic for wild-type human transthyretin: a possible model for senile systemic amyloidosis. Lab Invest. 2001;81(3):385–396. Copyright 2001.Citation88 (C) The human TTR protein structure; adapted from RCSB PDB https://www.rcsb.org/pdb/explore/remediatedSequence.do?structureId=5TZL of PDB ID 5TZL. Kabsch W, Sander C. (1983) Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers. 22(12); 2577–2637.Citation92
Figure 3 Mutations described in TTR gene. ATTR is caused by mutations in TTR gene the protein product of which is expressed mainly in the liver. There exist more than 100 mutations in TTR protein. From Alnylam Pharmaceuticals, Inc. Alnylam Pharmaceuticals discontinues revusiran development. 2016. Available from: http://investors.alnylam.com/releasedetail.cfm?ReleaseID=992320; with permission.Citation34
