PMID- 31752530
OWN - NLM
STAT- MEDLINE
DCOM- 20200521
LR  - 20230201
IS  - 1946-6544 (Electronic)
IS  - 1946-6536 (Print)
IS  - 1946-6536 (Linking)
VI  - 30
IP  - 6
DP  - 2019 Dec
TI  - Lot-to-Lot Variation in Adeno-Associated Virus Serotype 9 (AAV9) Preparations.
PG  - 214-225
LID - 10.1089/hgtb.2019.105 [doi]
AB  - Viral vectors are complex drugs that pose a particular challenge for 
      manufacturing. Previous studies have shown that, unlike small-molecule drugs, 
      vector preparations do not yield a collection of identical particles. Instead, a 
      mixture of particles that vary in capsid stoichiometry and impurities is created, 
      which may differ from lot to lot. The consequences of this are unclear, but 
      conflicting reports regarding the biological properties of vectors, including 
      transduction patterns, suggest that this variability may have an effect. However, 
      other variables, including differences in animal strains and techniques, make it 
      difficult to identify a cause. Here, we report lot-to-lot variation in spinal 
      cord gray matter transduction following intrathecal delivery of 
      self-complementary adeno-associated virus serotype 9 vectors. Eleven lots of 
      vector were evaluated from six vector cores, including one preclinical/Good 
      Laboratory Practice lot. Eight of the lots, including the preclinical lot, failed 
      to transduce the gray matter, whereas the other three provided robust 
      transduction. The cause for this variation is unknown, but it did not correlate 
      with vector titer, buffer, or purification method. These results highlight the 
      need to identify the cause of this variation and to develop improved production 
      and quality control methods to ensure lot-to-lot consistency of vector potency.
FAU - O'Connor, Deirdre M
AU  - O'Connor DM
AD  - Department of Neurosurgery, Emory University School of Medicine, Atlanta, 
      Georgia.
FAU - Lutomski, Corinne
AU  - Lutomski C
AD  - Chemistry, Indiana University Bloomington, Bloomington, Indiana.
FAU - Jarrold, Martin F
AU  - Jarrold MF
AD  - Chemistry, Indiana University Bloomington, Bloomington, Indiana.
FAU - Boulis, Nicholas M
AU  - Boulis NM
AD  - Department of Neurosurgery, Emory University School of Medicine, Atlanta, 
      Georgia.
FAU - Donsante, Anthony
AU  - Donsante A
AD  - Department of Neurosurgery, Emory University School of Medicine, Atlanta, 
      Georgia.
LA  - eng
GR  - R21 NS085553/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Hum Gene Ther Methods
JT  - Human gene therapy methods
JID - 101573202
SB  - IM
MH  - Animals
MH  - Dependovirus/*physiology
MH  - Genetic Vectors/chemistry/*metabolism
MH  - Gray Matter/metabolism
MH  - HEK293 Cells
MH  - Humans
MH  - Mass Spectrometry
MH  - Rats
MH  - Serogroup
MH  - Swine
MH  - Tissue Distribution
MH  - Transfection/methods/standards
PMC - PMC6919242
OTO - NOTNLM
OT  - AAV9
OT  - intrathecal
OT  - lot-to-lot variation
OT  - spinal cord
OT  - transduction
COIS- A.D. is an inventor on a patent regarding the use of AAV9 vectors in the central 
      nervous system.
EDAT- 2019/11/23 06:00
MHDA- 2020/05/22 06:00
PMCR- 2020/12/01
CRDT- 2019/11/23 06:00
PHST- 2019/11/23 06:00 [pubmed]
PHST- 2020/05/22 06:00 [medline]
PHST- 2019/11/23 06:00 [entrez]
PHST- 2020/12/01 00:00 [pmc-release]
AID - 10.1089/hgtb.2019.105 [pii]
AID - 10.1089/hgtb.2019.105 [doi]
PST - ppublish
SO  - Hum Gene Ther Methods. 2019 Dec;30(6):214-225. doi: 10.1089/hgtb.2019.105.