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hATTR therapies use different approaches to target TTR protein2

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Liver Icon
Liver2,3
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Transthyretin Tetramer Destabilizes
TTR tetramer dissociation
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Tetramer Dissociates Into Monomers
Monomers misfold
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Monomers Misfold And Aggregate Into Amyloid Fibrils
Amyloid fibril formation
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Amyloid Deposits Throughout The Body
Deposition
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A SILENCER TARGETS TTR mRNA2,4

TTR mRNA Degradation
TTR mRNA
DNA Silencerarrow icon
Silencer
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mRNA Targeted Degradation
mRNA-targeted degradation
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Reduced TTR Protein Levels
Reduced TTR protein levels
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A STABILIZER BINDS TO TTR TETRAMERS2,4,5

Unstable Tetramer
Unstable
tetramer
TTR Stabilizerarrow icon
Stabilizer
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Prevents Tetramer Dissociation
Prevents tetramer dissociation
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Reduced TTR Dissociation and Misfolding
Reduced TTR dissociation and misfolding
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A SILENCER
TARGETS TTR mRNA2,4

TTR mRNA
TTR mRNA
Silencer
Silencer
mRNA-targeted degradation
mRNA-targeted degradation
Reduced TTR protein levels
Reduced TTR protein levels
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A STABILIZER BINDS TO TTR TETRAMERS2,4,5

Unstable tetramer
Unstable tetramer
Silencer
Stabilizer
Prevents tetramer dissociation
Prevents tetramer dissociation
Reduced TTR dissociation and misfolding
Reduced TTR dissociation
and misfolding
Monomers misfold
Monomers misfold
Amyloid fibril formation
Amyloid fibril formation
Deposition
Deposition
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mRNA, messenger ribonucleic acid; TTR, transthyretin.

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References: 1. Adams D, Ando Y, Beirão JM, et al. Expert consensus recommendations to improve diagnosis of ATTR amyloidosis with polyneuropathy. J Neurol. 2021;268(6):2109-2122. 2. Tschöpe C, Elsanhoury A. Treatment of transthyretin amyloid cardiomyopathy: the current options, the future, and the challenges. J Clin Med. 2022;11(8):2148. 3. Ioannou A, Fontana M, Gillmore JD. RNA targeting and gene editing strategies for transthyretin amyloidosis. BioDrugs. 2023;37(2):127-142. 4. Garcia-Pavia P, Rapezzi C, Adler Y, et al. Diagnosis and treatment of cardiac amyloidosis: a position statement of the ESC Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2021;42(16):1554-1568. 5. Planté-Bordeneuve V, Said G. Familial amyloid polyneuropathy. Lancet Neurol. 2011;10(12):1086-1097.

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