Overcoming cellular barriers for RNA therapeutics

SF Dowdy - Nature biotechnology, 2017 - nature.com
RNA-based therapeutics, such as small-interfering (siRNAs), microRNAs (miRNAs),
antisense oligonucleotides (ASOs), aptamers, synthetic mRNAs and CRISPR–Cas9, have …

Non-coding RNAs as drug targets

M Matsui, DR Corey - Nature reviews Drug discovery, 2017 - nature.com
Most of the human genome encodes RNAs that do not code for proteins. These non-coding
RNAs (ncRNAs) may affect normal gene expression and disease progression, making them …

Single-dose gene-replacement therapy for spinal muscular atrophy

JR Mendell, S Al-Zaidy, R Shell… - … England Journal of …, 2017 - Mass Medical Soc
Background Spinal muscular atrophy type 1 (SMA1) is a progressive, monogenic motor
neuron disease with an onset during infancy that results in failure to achieve motor …

Nusinersen versus sham control in later-onset spinal muscular atrophy

E Mercuri, BT Darras, CA Chiriboga… - … England Journal of …, 2018 - Mass Medical Soc
Background Nusinersen is an antisense oligonucleotide drug that modulates pre–
messenger RNA splicing of the survival motor neuron 2 (SMN2) gene. It has been …

Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study

RS Finkel, CA Chiriboga, J Vajsar, JW Day, J Montes… - The Lancet, 2016 - thelancet.com
Background Nusinersen is a 2′-O-methoxyethyl phosphorothioate-modified antisense drug
being developed to treat spinal muscular atrophy. Nusinersen is specifically designed to …

Base editing rescue of spinal muscular atrophy in cells and in mice

M Arbab, Z Matuszek, KM Kray, A Du, GA Newby… - Science, 2023 - science.org
Spinal muscular atrophy (SMA), the leading genetic cause of infant mortality, arises from
survival motor neuron (SMN) protein insufficiency resulting from SMN1 loss. Approved …

Mechanisms and regulation of alternative pre-mRNA splicing

Y Lee, DC Rio - Annual review of biochemistry, 2015 - annualreviews.org
Precursor messenger RNA (pre-mRNA) splicing is a critical step in the posttranscriptional
regulation of gene expression, providing significant expansion of the functional proteome of …

Antisense oligonucleotides: the next frontier for treatment of neurological disorders

C Rinaldi, MJA Wood - Nature Reviews Neurology, 2018 - nature.com
Antisense oligonucleotides (ASOs) were first discovered to influence RNA processing and
modulate protein expression over two decades ago; however, progress translating these …

[HTML][HTML] Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: Interim efficacy and safety results from the Phase 2 NURTURE …

C Darryl, E Bertini, KJ Swoboda, WL Hwu… - Neuromuscular …, 2019 - Elsevier
Spinal muscular atrophy (SMA) is a neurodegenerative disease associated with severe
muscle atrophy and weakness in the limbs and trunk. We report interim efficacy and safety …

Recent progress in non-native nucleic acid modifications

LK McKenzie, R El-Khoury, JD Thorpe… - Chemical Society …, 2021 - pubs.rsc.org
While Nature harnesses RNA and DNA to store, read and write genetic information, the
inherent programmability, synthetic accessibility and wide functionality of these nucleic acids …