Pursuing Next Generation Nucleic Acid Therapies
Three Drivers of Superior Efficacy in Neuroscience
1
Higher Cell Uptake, Leading to
Higher Potency at Same Dose
SNA
Linear
OLIGO DAPI
OLIGO DAPI
Superior cell uptake¹ vs. linear oligonucleotide with
SNA detection observed across multiple cell types
Broad CNS Penetration and
Uptake in all Neuronal Cells
Nucleus
(hematoxylin)
2
anti-MALAT1
ON probe
Deep Cerebellum
In Situ Hybridization of SNA in
the Brain (Rat) via ICM dosing
SNAS² reach deep brain regions and achieve
uptake in neurons, microglia and astrocytes
3
Higher Persistence in the CNS,
Leading to Prolonged Efficacy
Nusinersen
Alone
SNA-
Nusinersen
Radiolabeled biodistribution shows SNAs³ stay longer
in the CNS compared to linear nucleotide therapeutic
1) In vitro comparison in cortical neurons testing MALAT1 knockdown with IC 50 for SNA (141 nM) and linear oligonucleotide (464 nM), 2) In vivo testing with MALAT1 knockdown via intracisterna magna (ICM) route of administration 3) In vivo
comparison of rats dosed intrathecally with comparison shown at seven days after one-time administration.
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