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DOI 10.1016/j.celrep.2025.115730

Медицинская библиотека · Cell reports · 2025

Enhancer AAVs for targeting spinal motor neurons and descending motor pathways in rodents and macaque.

Kussick Emily, Johansen Nelson, Taskin Naz, Chowdhury Ananya, Quinlan Meagan A, Fraser Alex, Clark Andrew G, Wynalda Brooke, Martinez Refugio, Groce Erin L, Reding Melissa, Liang Elizabeth, Shulga Lyudmila, Huang Cindy, Casper Tamara, Clark Michael, Ho Windy, Gao Yuan, van Velthoven Cindy T J, Sobieski Cassandra, Ferrer Rebecca, Berg Melissa R, Curtis Britni C, English Chris, Day Jesse C, Fortuna Michal G, Donadio Nicholas, Newman Dakota, Yao Shenqin, Chakka Anish Bhaswanth, Goldy Jeff, Torkelson Amy, Guzman Junitta B, Chakrabarty Rushil, Nguy Beagen, Guilford Nathan, Pham Trangthanh H, Wright Vonn, Ronellenfitch Kara, Naidoo Robyn, Kenney Jaimie, Williford Ali, Ramakrishnan Charu, Drinnenberg Antonia, Gudsnuk Kathryn, Thyagarajan Bargavi, Smith Kimberly A, Dee Nick, Deisseroth Karl, Zeng Hongkui, Yao Zizhen, Tasic Bosiljka, Levi Boaz P, Hodge Rebecca, Bakken Trygve E, Lein Ed S, Ting Jonathan T, Daigle Tanya L

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Аннотация

Experimental access to cell types within the mammalian spinal cord is severely limited by the availability of genetic tools. To enable access to spinal motor neurons (SMNs) and SMN subtypes, we generated single-cell multiome datasets from mouse and macaque spinal cords and discovered putative enhancers for each neuronal population. We cloned these enhancers into adeno-associated viral vectors driving a reporter fluorophore and functionally screened them in the mouse. We extensively characterized the most promising candidate enhancers in rat and macaque and developed an optimized pan-SMN enhancer virus. Additionally, we generated derivative viruses expressing iCre297T recombinase or ChR2-EYFP for labeling and functional studies, and we created a single vector with combined enhancer elements to achieve simultaneous labeling of layer 5 extratelencephalic projecting neurons and SMNs. This unprecedented SMN toolkit will enable future investigations of cell type function across species and potential therapeutic interventions for human neurodegenerative diseases.

Для цитирования: Kussick Emily, Johansen Nelson, Taskin Naz, Chowdhury Ananya, Quinlan Meagan A, Fraser Alex, Clark Andrew G, Wynalda Brooke, Martinez Refugio, Groce Erin L, Reding Melissa, Liang Elizabeth, Shulga Lyudmila, Huang Cindy, Casper Tamara, Clark Michael, Ho Windy, Gao Yuan, van Velthoven Cindy T J, Sobieski Cassandra, Ferrer Rebecca, Berg Melissa R, Curtis Britni C, English Chris, Day Jesse C, Fortuna Michal G, Donadio Nicholas, Newman Dakota, Yao Shenqin, Chakka Anish Bhaswanth, Goldy Jeff, Torkelson Amy, Guzman Junitta B, Chakrabarty Rushil, Nguy Beagen, Guilford Nathan, Pham Trangthanh H, Wright Vonn, Ronellenfitch Kara, Naidoo Robyn, Kenney Jaimie, Williford Ali, Ramakrishnan Charu, Drinnenberg Antonia, Gudsnuk Kathryn, Thyagarajan Bargavi, Smith Kimberly A, Dee Nick, Deisseroth Karl, Zeng Hongkui, Yao Zizhen, Tasic Bosiljka, Levi Boaz P, Hodge Rebecca, Bakken Trygve E, Lein Ed S, Ting Jonathan T, Daigle Tanya L. Enhancer AAVs for targeting spinal motor neurons and descending motor pathways in rodents and macaque.. Cell reports. 2025. DOI: 10.1016/j.celrep.2025.115730.

Предметные рубрики MeSH

AnimalsMotor NeuronsDependovirusMiceSpinal CordRatsEnhancer Elements, GeneticGenetic VectorsMacacaHumans
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