The atlas of RNase H antisense oligonucleotide distribution and activity in the CNS of rodents and non-human primates following central administration

被引:70
作者
Jafar-nejad, Paymaan [1 ]
Powers, Berit [1 ]
Soriano, Armand [1 ]
Zhao, Hien [1 ]
Norris, Daniel A. [1 ]
Matson, John [1 ]
DeBrosse-Serra, Beatrice [1 ]
Watson, Jamie [1 ]
Narayanan, Padmakumar [1 ]
Chun, Seung J. [1 ]
Mazur, Curt [1 ]
Kordasiewicz, Holly [1 ]
Swayze, Eric E. [1 ]
Rigo, Frank [1 ]
机构
[1] Ionis Pharmaceut Inc, Carlsbad, CA 92010 USA
关键词
D O I
10.1093/nar/gkaa1235
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Antisense oligonucleotides (ASOs) have emerged as a new class of drugs to treat a wide range of diseases, including neurological indications. Spinraza, an ASO that modulates splicing of SMN2 RNA, has shown profound disease modifying effects in Spinal Muscular Atrophy (SMA) patients, energizing efforts to develop ASOs for other neurological diseases. While SMA specifically affects spinal motor neurons, other neurological diseases affect different central nervous system (CNS) regions, neuronal and nonneuronal cells. Therefore, it is important to characterize ASO distribution and activity in all major CNS structures and cell types to have a better understanding of which neurological diseases are amenable to ASO therapy. Here we present for the first time the atlas of ASO distribution and activity in the CNS of mice, rats, and non-human primates (NHP), species commonly used in preclinical therapeutic development. Following central administration of an ASO to rodents, we observe widespread distribution and target RNA reduction throughout the CNS in neurons, oligodendrocytes, astrocytes and microglia. This is also the case in NHP, despite a larger CNS volume and more complex neuroarchitecture. Our results demonstrate that ASO drugs are well suited for treating a wide range of neurological diseases for which no effective treatments are available.
引用
收藏
页码:657 / 673
页数:17
相关论文
共 53 条
[31]   Spinal muscular atrophy: A deficiency in a ubiquitous protein; a motor neuron-specific disease [J].
Monani, UR .
NEURON, 2005, 48 (06) :885-896
[32]   Antisense oligonucleotides targeting mutant Ataxin-7 restore visual function in a mouse model of spinocerebellar ataxia type 7 [J].
Niu, Chenchen ;
Prakash, Thazah P. ;
Kim, Aneeza ;
Quach, John L. ;
Huryn, Laryssa A. ;
Yang, Yuechen ;
Lopez, Edith ;
Jazayeri, Ali ;
Hung, Gene ;
Sopher, Bryce L. ;
Brooks, Brian P. ;
Swayze, Eric E. ;
Bennett, C. Frank ;
La Spada, Albert R. .
SCIENCE TRANSLATIONAL MEDICINE, 2018, 10 (465)
[33]   Pharmacokinetics of an intracerebroventricularly administered antibody in rats [J].
Noguchi, Yuki ;
Kato, Motohiro ;
Ozeki, Kazuhisa ;
Ishigai, Masaki .
MABS, 2017, 9 (07) :1210-1215
[34]   Comprehensive Structure-Activity Relationship of Triantennary N-Acetylgalactosamine Conjugated Antisense Oligonucleotides for Targeted Delivery to Hepatocytes [J].
Prakash, Thazha P. ;
Yu, Jinghua ;
Migawa, Michael T. ;
Kinberger, Garth A. ;
Wan, W. Brad ;
Ostergaard, Michael E. ;
Carty, Recaldo L. ;
Vasquez, Guillermo ;
Low, Audrey ;
Chappell, Alfred ;
Schmidt, Karsten ;
Aghajan, Mariam ;
Crosby, Jeff ;
Murray, Heather M. ;
Booten, Sheri L. ;
Hsiao, Jill ;
Soriano, Armand ;
Machemer, Todd ;
Cauntay, Patrick ;
Burel, Sebastien A. ;
Murray, Susan F. ;
Gaus, Hans ;
Graham, Mark J. ;
Swayze, Eric E. ;
Seth, Punit P. .
JOURNAL OF MEDICINAL CHEMISTRY, 2016, 59 (06) :2718-2733
[35]   Age-dependent SMN expression in disease-relevant tissue and implications for SMA treatment [J].
Ramos, Daniel M. ;
d'Ydewalle, Constantin ;
Gabbeta, Vijayalakshmi ;
Dakka, Amal ;
Klein, Stephanie K. ;
Norris, Daniel A. ;
Matson, John ;
Taylor, Shannon J. ;
Zaworski, Phillip G. ;
Prior, Thomas W. ;
Snyder, Pamela J. ;
Valdivia, David ;
Hatem, Christine L. ;
Waters, Ian ;
Gupte, Nikhil ;
Swoboda, Kathryn J. ;
Rigo, Frank ;
Bennett, C. Frank ;
Naryshkin, Nikolai ;
Paushkin, Sergey ;
Crawford, Thomas O. ;
Sumner, Charlotte J. .
JOURNAL OF CLINICAL INVESTIGATION, 2019, 129 (11) :4817-4831
[36]   Antisense oligonucleotides extend survival of prion-infected mice [J].
Raymond, Gregory J. ;
Zhao, Hien Tran ;
Race, Brent ;
Raymond, Lynne D. ;
Williams, Katie ;
Swayze, Eric E. ;
Graffam, Samantha ;
Le, Jason ;
Caron, Tyler ;
Stathopoulos, Jacquelyn ;
O'Keefe, Rhonda ;
Lubke, Lori L. ;
Reidenbach, Andrew G. ;
Kraus, Allison ;
Schreiber, Stuart L. ;
Mazur, Curt ;
Cabin, Deborah E. ;
Carroll, Jeffrey B. ;
Minikel, Eric Vallabh ;
Kordasiewicz, Holly ;
Caughey, Byron ;
Vallabh, Sonia M. .
JCI INSIGHT, 2019, 4 (16)
[37]   Pharmacology of a Central Nervous System Delivered 2′-O-Methoxyethyl-Modified Survival of Motor Neuron Splicing Oligonucleotide in Mice and Nonhuman Primates [J].
Rigo, Frank ;
Chun, Seung J. ;
Norris, Daniel A. ;
Hung, Gene ;
Lee, Sam ;
Matson, John ;
Fey, Robert A. ;
Gaus, Hans ;
Hua, Yimin ;
Grundy, John S. ;
Krainer, Adrian R. ;
Henry, Scott P. ;
Bennett, C. Frank .
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2014, 350 (01) :46-55
[38]   Selective tissue targeting of synthetic nucleic acid drugs [J].
Seth, Punit P. ;
Tanowitz, Michael ;
Bennett, C. Frank .
JOURNAL OF CLINICAL INVESTIGATION, 2019, 129 (03) :915-925
[39]   Antisense oligonucleotide therapy for neurodegenerative disease [J].
Smith, Richard A. ;
Miller, Timothy M. ;
Yamanaka, Koji ;
Monia, Brett P. ;
Condon, Thomas F. ;
Hung, Gene ;
Lobsiger, Christian S. ;
Ward, Chris M. ;
McAlonis-Downes, Melissa ;
Wei, Hongbing ;
Wancewicz, Ed V. ;
Bennett, C. Frank ;
Cleveland, Don W. .
JOURNAL OF CLINICAL INVESTIGATION, 2006, 116 (08) :2290-2296
[40]   Huntingtin suppression restores cognitive function in a mouse model of Huntington's disease [J].
Southwell, Amber L. ;
Kordasiewicz, Holly B. ;
Langbehn, Douglas ;
Skotte, Niels H. ;
Parsons, Matthew P. ;
Villanueva, Erika B. ;
Caron, Nicholas S. ;
Ostergaard, Michael E. ;
Anderson, Lisa M. ;
Xie, Yuanyun ;
Dal Cengio, Louisa ;
Findlay-Black, Hailey ;
Doty, Crystal N. ;
Fitsimmons, Bethany ;
Swayze, Eric E. ;
Seth, Punit P. ;
Raymond, Lynn A. ;
Bennett, C. Frank ;
Hayden, Michael R. .
SCIENCE TRANSLATIONAL MEDICINE, 2018, 10 (461)