PMID- 38385340
OWN - NLM
STAT- MEDLINE
DCOM- 20240502
LR  - 20240502
IS  - 1533-1601 (Electronic)
IS  - 0192-6233 (Linking)
VI  - 52
IP  - 1
DP  - 2024 Jan
TI  - Adeno-Associated Virus-Mediated Dorsal Root Ganglion Toxicity in the New Zealand 
      White Rabbit.
PG  - 35-54
LID - 10.1177/01926233241229808 [doi]
AB  - Recombinant adeno-associated virus (AAV)-mediated degeneration of sensory neurons 
      in the dorsal root ganglia (DRG) and trigeminal ganglia (TG) has been observed in 
      non-human primates (NHPs) following intravenous (IV) and intrathecal (IT) 
      delivery. Administration of recombinant AAV encoding a human protein transgene 
      via a single intra-cisterna magna (ICM) injection in New Zealand white rabbits 
      resulted in histopathology changes very similar to NHPs: mononuclear cell 
      infiltration, degeneration/necrosis of sensory neurons, and nerve fiber 
      degeneration of sensory tracts in the spinal cord and of multiple nerves. 
      AAV-associated clinical signs and incidence/severity of histologic findings 
      indicated that rabbits were equally or more sensitive than NHPs to sensory neuron 
      damage. Another study using human and rabbit transgene constructs of the same 
      protein demonstrated comparable changes suggesting that the effects are not an 
      immune response to the non-self protein transgene. Rabbit has not been 
      characterized as a species for general toxicity testing of AAV gene therapies, 
      but these studies suggest that it may be an alternative model to investigate 
      mechanisms of AAV-mediated neurotoxicity and test novel AAV designs mitigating 
      these adverse effects.
FAU - Tien, Eric
AU  - Tien E
AUID- ORCID: 0009-0005-8213-1657
AD  - Biogen Inc., Cambridge, Massachusetts, USA.
FAU - Grubor, Branka
AU  - Grubor B
AUID- ORCID: 0000-0003-2510-7499
AD  - Biogen Inc., Cambridge, Massachusetts, USA.
FAU - Kirkland, Melissa
AU  - Kirkland M
AD  - Biogen Inc., Cambridge, Massachusetts, USA.
FAU - Chan, Su Jing
AU  - Chan SJ
AD  - Voyager Therapeutics, Inc., Lexington, Massachusetts, USA.
FAU - van der Munnik, Nick
AU  - van der Munnik N
AD  - GlaxoSmithKline, Middlesex, UK.
FAU - Xu, Wenlong
AU  - Xu W
AD  - Sonata Therapeutics, Watertown, Massachusetts, USA.
FAU - Henry, Kate
AU  - Henry K
AD  - Biogen Inc., Cambridge, Massachusetts, USA.
FAU - Hamann, Stefan
AU  - Hamann S
AD  - Biogen Inc., Cambridge, Massachusetts, USA.
FAU - Wei, Cong
AU  - Wei C
AD  - Biogen Inc., Cambridge, Massachusetts, USA.
FAU - Lee, Wan-Hung
AU  - Lee WH
AUID- ORCID: 0000-0002-5030-2619
AD  - Biogen Inc., Cambridge, Massachusetts, USA.
FAU - Gianni, Davide
AU  - Gianni D
AD  - Biogen Inc., Cambridge, Massachusetts, USA.
FAU - Brennecke, Ashton
AU  - Brennecke A
AD  - Biogen Inc., Cambridge, Massachusetts, USA.
FAU - Nambiar, Kalyani
AU  - Nambiar K
AD  - Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA.
FAU - Chen, Jeron
AU  - Chen J
AD  - Voyager Therapeutics, Inc., Lexington, Massachusetts, USA.
FAU - Liu, Bin
AU  - Liu B
AD  - Vertex, Boston, Massachusetts, USA.
FAU - Shen, Shen
AU  - Shen S
AD  - Vertex, Boston, Massachusetts, USA.
FAU - Tremblay, Claudine
AU  - Tremblay C
AD  - Charles River Laboratories, Montreal, Quebec, Canada.
FAU - Plowey, Edward D
AU  - Plowey ED
AD  - Biogen Inc., Cambridge, Massachusetts, USA.
FAU - Trapa, Patrick
AU  - Trapa P
AD  - Biogen Inc., Cambridge, Massachusetts, USA.
FAU - Fikes, James
AU  - Fikes J
AUID- ORCID: 0000-0002-5837-7359
AD  - Biogen Inc., Cambridge, Massachusetts, USA.
FAU - Suh, Junghae
AU  - Suh J
AD  - Biogen Inc., Cambridge, Massachusetts, USA.
FAU - Morris, Dale
AU  - Morris D
AD  - Biogen Inc., Cambridge, Massachusetts, USA.
LA  - eng
PT  - Journal Article
DEP - 20240222
PL  - United States
TA  - Toxicol Pathol
JT  - Toxicologic pathology
JID - 7905907
SB  - IM
MH  - Animals
MH  - Rabbits
MH  - *Ganglia, Spinal
MH  - *Dependovirus/genetics
MH  - Genetic Vectors
MH  - Male
MH  - Humans
MH  - Transgenes
MH  - Female
MH  - Sensory Receptor Cells
OTO - NOTNLM
OT  - AAV
OT  - dorsal root ganglia
OT  - gene therapy
OT  - toxicity
COIS- Declaration of Conflicting InterestsThe author(s) declared the following 
      potential conflicts of interest with respect to the research, authorship, and/or 
      publication of this article: All authors were employed by Biogen (except for 
      Claudine Tremblay) at the time of their contribution to this work.
EDAT- 2024/02/22 12:43
MHDA- 2024/05/02 13:00
CRDT- 2024/02/22 07:48
PHST- 2024/05/02 13:00 [medline]
PHST- 2024/02/22 12:43 [pubmed]
PHST- 2024/02/22 07:48 [entrez]
AID - 10.1177/01926233241229808 [doi]
PST - ppublish
SO  - Toxicol Pathol. 2024 Jan;52(1):35-54. doi: 10.1177/01926233241229808. Epub 2024 
      Feb 22.