| 000 | 02528 am a22003253u 4500 | ||
|---|---|---|---|
| 042 | _adc | ||
| 100 | 1 | 0 |
_aHammond, Suzan M. _eauthor _92385 |
| 700 | 1 | 0 |
_aAbendroth, Frank _eauthor _92386 |
| 700 | 1 | 0 |
_aGoli, Larissa _eauthor _92387 |
| 700 | 1 | 0 |
_aStoodley, Jessica _eauthor _92388 |
| 700 | 1 | 0 |
_aBurrell, Matthew _eauthor _92389 |
| 700 | 1 | 0 |
_aThom, George _eauthor _92390 |
| 700 | 1 | 0 |
_aGurrell, Ian _eauthor _92391 |
| 700 | 1 | 0 |
_aAhlskog, Nina _eauthor _92392 |
| 700 | 1 | 0 |
_aGait, Michael J. _eauthor _92393 |
| 700 | 1 | 0 |
_aWood, Matthew J.A. _eauthor _92394 |
| 700 | 1 | 0 |
_aWebster, Carl I. _eauthor _92395 |
| 245 | 0 | 0 | _aAntibody-oligonucleotide conjugate achieves CNS delivery in animal models for spinal muscular atrophy |
| 260 |
_bAmerican Society for Clinical Investigation, _c2022-12-22. |
||
| 500 | _a/pmc/articles/PMC7614086/ | ||
| 500 | _a/pubmed/36346674 | ||
| 520 | _aAntisense 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 | _a© 2022 Hammond et al. | ||
| 540 | _ahttps://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 | _aen | ||
| 690 |
_aResearch Article _91689 |
||
| 655 | 7 |
_aText _2local |
|
| 786 | 0 | _nJCI Insight | |
| 856 | 4 | 1 |
_uhttp://dx.doi.org/10.1172/jci.insight.154142 _zConnect to this object online. |
| 999 |
_c1954 _d1954 |
||