Antibody-oligonucleotide conjugate achieves CNS delivery in animal models for spinal muscular atrophy (Record no. 1954)
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042 ## - AUTHENTICATION CODE | |
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Authentication code | dc |
100 10 - MAIN ENTRY--PERSONAL NAME | |
Personal name | Hammond, Suzan M. |
Relator term | author |
9 (RLIN) | 2385 |
245 00 - TITLE STATEMENT | |
Title | Antibody-oligonucleotide conjugate achieves CNS delivery in animal models for spinal muscular atrophy |
260 ## - PUBLICATION, DISTRIBUTION, ETC. | |
Name of publisher, distributor, etc. | American Society for Clinical Investigation, |
Date of publication, distribution, etc. | 2022-12-22. |
500 ## - GENERAL NOTE | |
General note | /pmc/articles/PMC7614086/ |
500 ## - GENERAL NOTE | |
General note | /pubmed/36346674 |
520 ## - SUMMARY, ETC. | |
Summary, etc. | Antisense oligonucleotides (ASOs) have emerged as one of the most innovative new genetic drug modalities. However, their high molecular weight limits their bioavailability for otherwise-treatable neurological disorders. We investigated conjugation of ASOs to an antibody against the murine transferrin receptor, 8D3(130), and evaluated it via systemic administration in mouse models of the neurodegenerative disease spinal muscular atrophy (SMA). SMA, like several other neurological and neuromuscular diseases, is treatable with single-stranded ASOs that modulate splicing of the survival motor neuron 2 (SMN2) gene. Administration of 8D3(130)-ASO conjugate resulted in elevated levels of bioavailability to the brain. Additionally, 8D3(130)-ASO yielded therapeutic levels of SMN2 splicing in the central nervous system of adult human SMN2-transgenic (hSMN2-transgenic) mice, which resulted in extended survival of a severely affected SMA mouse model. Systemic delivery of nucleic acid therapies with brain-targeting antibodies offers powerful translational potential for future treatments of neuromuscular and neurodegenerative diseases. |
540 ## - TERMS GOVERNING USE AND REPRODUCTION NOTE | |
Terms governing use and reproduction | © 2022 Hammond et al. |
540 ## - TERMS GOVERNING USE AND REPRODUCTION NOTE | |
Terms governing use and reproduction | https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
546 ## - LANGUAGE NOTE | |
Language note | en |
690 ## - LOCAL SUBJECT ADDED ENTRY--TOPICAL TERM (OCLC, RLIN) | |
Topical term or geographic name as entry element | Research Article |
9 (RLIN) | 1689 |
655 7# - INDEX TERM--GENRE/FORM | |
Genre/form data or focus term | Text |
Source of term | local |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Abendroth, Frank |
Relator term | author |
9 (RLIN) | 2386 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Goli, Larissa |
Relator term | author |
9 (RLIN) | 2387 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Stoodley, Jessica |
Relator term | author |
9 (RLIN) | 2388 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Burrell, Matthew |
Relator term | author |
9 (RLIN) | 2389 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Thom, George |
Relator term | author |
9 (RLIN) | 2390 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Gurrell, Ian |
Relator term | author |
9 (RLIN) | 2391 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Ahlskog, Nina |
Relator term | author |
9 (RLIN) | 2392 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Gait, Michael J. |
Relator term | author |
9 (RLIN) | 2393 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Wood, Matthew J.A. |
Relator term | author |
9 (RLIN) | 2394 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Webster, Carl I. |
Relator term | author |
9 (RLIN) | 2395 |
786 0# - DATA SOURCE ENTRY | |
Note | JCI Insight |
856 41 - ELECTRONIC LOCATION AND ACCESS | |
Uniform Resource Identifier | <a href="http://dx.doi.org/10.1172/jci.insight.154142">http://dx.doi.org/10.1172/jci.insight.154142</a> |
Public note | Connect to this object online. |
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