The paper identifies a spatial coordination between mRNA initiation and termination sites, proposing a 'Positional Initiation-Termination Axis' that influences isoform diversity.

Science · Oct 9, 2025Peer-reviewedGenomics

Preventing acute neurotoxicity of CNS therapeutic oligonucleotides with the addition of Ca2+ and Mg2+ in the formulation

Rachael Miller, Joseph D. Paquette, Alexandra Barker, Ellen Sapp, Nicholas McHugh, Brianna M. Bramato, Nozomi Yamada, Julia F. Alterman, Dimas Echeverria, Ken Yamada, Jonathan K. Watts, Christelle Anaclet, Marian DiFiglia, Anastasia Khvorova, Neil Aronin M. D

This study shows adding high concentrations of Ca2+ and Mg2+ to oligonucleotide formulations prevents acute neurotoxicity in CNS delivery without affecting efficacy.

Molecular Therapy — Nucleic Acids · Oct 15, 2024Peer-reviewedNeuroscience

mRNA nuclear clustering leads to a difference in mutant huntingtin mRNA and protein silencing by siRNAs in vivo

Sarah E. Allen, Daniel O’Reilly, Rachael Miller, Ellen Sapp, Ashley Summers, Joseph D. Paquette, Dimas Echeverria, Brianna M. Bramato, Nicholas McHugh, Ken Yamada, Neil Aronin M. D, Marian DiFiglia, Anastasia Khvorova

The paper shows that di-valent siRNA reduces wild-type Htt mRNA but not mutant HTT mRNA in HD mouse models, with mutant transcripts remaining clustered in the nucleus.

Nucleic Acid Therapeutics · Jul 18, 2024Peer-reviewedNeuroscience