Back

Harnessing Synaptic Vesicle Release and Recycling Mechanism for Molecule Delivery to Neurons

Yee, K. K.; Kumamoto, J.; Inomata, D.; Suzuki, N.; Harada, R.; Yumoto, N.

2024-09-12 neuroscience
10.1101/2024.09.11.612569 bioRxiv
Show abstract

Neurodegenerative clinical trials often fail due to insufficient drug doses in reaching targeted cells and the unintended delivery to non-targeted cells. This study demonstrates an alternative neuron-selective drug delivery system, which utilizes the synaptic vesicle release and recycling mechanism (SVRM) by antibody shuttles targeting synaptic vesicle transmembrane proteins for molecule delivery. Using Synaptotagmin-2 (SYT2), we exemplify that intravenously administered anti-SYT2 antibodies localize to neuromuscular junctions, undergo uptake, and retrograde transport to ChAT-positive motor neurons (MNs) in the spinal cord and brainstem. The delivery of anti-microtubule agent and Malat1 gapmer antisense oligonucleotide to MNs with anti-SYT2 antibodies induces axon degeneration and reduction of Malat1 RNA expression, respectively. This approach circumvents the blood-spinal cord barrier, enabling selective delivery of therapeutic molecules to neurons while minimizing effects in non-targeted cells. Thus harnessing SVRM presents a promising strategy for enhancing drug concentrations in neurons and improving treatment efficacy for neurodegenerative diseases.

Matching journals

The top 9 journals account for 50% of the predicted probability mass.

1
Cell Reports
○ 1498 papers in training set
Top 2%
9.7%
Similar papers in this journal
2
Molecular Therapy
○ 81 papers in training set
Top 0.2%
7.9%
Similar papers in this journal
3
iScience
○ 1154 papers in training set
Top 1.0%
6.8%
Similar papers in this journal
4
Nature Communications
○ 5641 papers in training set
Top 25%
6.3%
Similar papers in this journal
5
Scientific Reports
○ 3612 papers in training set
Top 19%
4.9%
Similar papers in this journal
6
Theranostics
● 37 papers in training set
Top 0.1%
4.1%
7
Molecular Therapy Nucleic Acids
○ 39 papers in training set
Top 0.2%
4.1%
8
Brain
◐ 168 papers in training set
Top 1%
3.5%
9
Frontiers in Molecular Neuroscience
○ 47 papers in training set
Top 0.2%
3.2%
50% of probability mass above
10
Cell Reports Methods
○ 165 papers in training set
Top 0.7%
2.8%
11
eLife
● 5828 papers in training set
Top 45%
2.1%
12
Science Advances
● 1243 papers in training set
Top 16%
2.1%
13
Journal of Controlled Release
○ 44 papers in training set
Top 0.4%
2.1%
14
Neuron
○ 337 papers in training set
Top 3%
1.7%
15
Advanced Science
○ 286 papers in training set
Top 4%
1.7%
16
ACS Nano
● 113 papers in training set
Top 1%
1.7%
17
Proceedings of the National Academy of Sciences
● 2444 papers in training set
Top 28%
1.7%
18
ACS Chemical Neuroscience
● 67 papers in training set
Top 0.9%
1.3%
19
Signal Transduction and Targeted Therapy
○ 30 papers in training set
Top 0.3%
1.3%
20
Advanced Healthcare Materials
○ 85 papers in training set
Top 1%
1.1%
21
Cell Reports Medicine
○ 153 papers in training set
Top 3%
1.1%
22
Advanced Therapeutics
○ 17 papers in training set
Top 0.2%
1.1%
23
npj Parkinson's Disease
○ 105 papers in training set
Top 1%
1.0%
24
Science China Life Sciences
○ 29 papers in training set
Top 0.5%
1.0%
25
PLOS ONE
● 5266 papers in training set
Top 56%
1.0%
26
Cell Death & Disease
147 papers in training set
Top 4%
0.8%
27
Journal of Neurochemistry
○ 53 papers in training set
Top 1%
0.8%
28
Fluids and Barriers of the CNS
○ 28 papers in training set
Top 0.5%
0.8%
29
eBioMedicine
○ 183 papers in training set
Top 6%
0.8%
30
Biomaterials
○ 84 papers in training set
Top 2%
0.8%

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.