hATTR therapies use different approaches to target TTR protein2
Liver2,3
TTR tetramer dissociation
Monomers misfold
Amyloid fibril formation
Deposition
A SILENCER TARGETS TTR mRNA2,4
TTR mRNA
Silencer
mRNA-targeted degradation
Reduced TTR protein levels
A STABILIZER BINDS TO TTR TETRAMERS2,4,5
Unstable
tetramer
tetramer
Stabilizer
Prevents tetramer dissociation
Reduced TTR dissociation and misfolding
A SILENCER
TARGETS TTR mRNA2,4
TTR mRNA
Silencer
mRNA-targeted degradation
Reduced TTR protein levels
A STABILIZER BINDS TO TTR TETRAMERS2,4,5
Unstable tetramer
Stabilizer
Prevents tetramer dissociation
Reduced TTR dissociation
and misfolding
and misfolding
Monomers misfold
Amyloid fibril formation
Deposition
mRNA, messenger ribonucleic acid; TTR, transthyretin.
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