Paymaan Jafar‐Nejad

This paper develops a VHH-Fc fusion protein to deliver siRNAs and ASOs across the BBB in rodents and NHPs, showing that binding affinity, DAR, and conjugation site affect delivery efficiency.

This paper introduces NMA-modified antisense oligonucleotides that show improved potency compared to MOE-modified SSOs in modulating splicing for SMA and Dravet syndrome.

This study shows that NMNAT2 loss disrupts APP processing in neurons by causing redox failure and proteostasis disruption, with SARM1 playing a key role in this process.

The paper identifies a disrupted mitochondrial-purine metabolism link in MECP2 Duplication Syndrome across multiple models, linking it to neurodevelopmental issues.

A splice-switching antisense oligonucleotide delivered via intravitreal injection mitigates early retinal dysfunction in a pig model of CLN3 Batten disease.

The paper shows that TDP-43 pathology causes a cryptic exon in G3BP1 to be included in neurons, leading to a protein that disrupts stress granule dynamics in ALS/FTD.

The paper assesses the cell-type-specific activity of intrathecally delivered antisense oligonucleotides in deep brain regions of non-human primates, finding broad target engagement across neuronal and non-neuronal cells.

This study shows that antisense oligonucleotides targeting VCP reduce disease pathology and improve muscle function in cell and mouse models of multisystem proteinopathy.

This study shows that ASO-mediated Gys1 knockdown in a mouse model of Pompe disease reduces glycogen accumulation and improves motor function, both alone and in combination with ERT.

This study characterizes an acute sedation response caused by phosphorothioate ASOs after CNS delivery, showing it is sequence-, dose-, and chemistry-dependent and can be mitigated.

The paper characterizes a transient neurobehavioral response to high-dose oligonucleotide delivery in the CNS and provides a framework to mitigate it through magnesium supplementation.

This study investigates the role of mTORC2 in SLE and shows that targeting mTORC2 reduces immunopathology in both mouse models and human PBMCs.

This study investigates the role of antisense and sense repeat RNAs in producing dipeptide repeat proteins in C9ORF72 expansion carriers and shows that targeting sense RNA with ASOs reduces both sense- and antisense-dependent DPR proteins.

This study shows that reducing RAD23A in TDP-43 mice improves survival, behavior, and reduces TDP-43 pathology and transcriptomic alterations.

This paper demonstrates that transient suppression of PTBP1 in aged glial cells can re-activate neurogenesis in murine and human brains, generating new neurons through canonical pathways.

This study shows that antisense oligonucleotides can increase progranulin protein levels by blocking miR-29b binding in GRN mRNA, offering a potential therapy for FTD.

This study shows that reducing Nemo-like kinase enhances lysosome biogenesis and improves TDP-43 clearance, alleviating neurodegeneration in mouse models.

This study shows that targeting G2C4 antisense repeat RNA, not G4C2 sense RNA, mitigates TDP-43 dysfunction in C9orf72 ALS/FTD patient neurons, explaining the failure of previous G4C2 ASO clinical trials.

This study identifies early activation of stress and apoptotic pathways in a mouse model of ALS/FTD and shows that suppressing Chop has limited effects on disease progression.

This study shows that reducing Ube3a-ATS with antisense oligonucleotides rescues EEG rhythms and sleep in Angelman syndrome mouse models, suggesting a broader therapeutic window than previously believed.

This study demonstrates that antisense oligonucleotide therapy reduces seizures and improves survival in a KCNT1 mouse model of encephalopathy.

This study shows NMNAT2 maintains NAD redox potential in axons to support glycolysis and fast transport, preventing axonal degeneration in mice.

This study identifies PFTK1's role in axogenesis by regulating RhoA phosphorylation and activity during CNS development in Drosophila and mice.

This study shows that antisense oligonucleotides targeting UBE3A-ATS restore UBE3A expression by removing transcriptional interference in Angelman syndrome neurons.

The paper maps ASO distribution and activity in the CNS of rodents and NHP after central administration, showing widespread effects across cell types.

This study shows that reducing SCN2A function with an antisense oligonucleotide improves survival and behavior in a mouse model of early seizure onset DEE.