AAV2 capsid clearance and neuronal trafficking dynamics in the central nervous system

Samulski RJ, Berns KI, Tan M, Muzyczka N. Cloning of adeno-associated virus into pBR322: rescue of intact virus from the recombinant plasmid in human cells. Proc Natl Acad Sci USA. 1982;79:2077–81.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kaplitt MG, Leone P, Samulski RJ, Xiao X, Pfaff DW, O’Malley KL, et al. Long-term gene expression and phenotypic correction using adeno-associated virus vectors in the mammalian brain. Nat Genet. 1994;8:148–54.

Article  CAS  PubMed  Google Scholar 

McCown TJ, Xiao X, Li J, Breese GR, Samulski RJ. Differential and persistent expression patterns of CNS gene transfer by an adeno-associated virus (AAV) vector. Brain Res. 1996;713:99–107.

Article  CAS  PubMed  Google Scholar 

Kaplitt MG, Feigin A, Tang C, Fitzsimons HL, Mattis P, Lawlor PA, et al. Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinson’s disease: an open label, phase I trial. Lancet. 2007;369:2097–105.

Article  CAS  PubMed  Google Scholar 

Bishop KM, Hofer EK, Mehta A, Ramirez A, Sun L, Tuszynski M, et al. Therapeutic potential of CERE-110 (AAV2-NGF): targeted, stable, and sustained NGF delivery and trophic activity on rodent basal forebrain cholinergic neurons. Exp Neurol. 2008;211:574–84.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Marks WJ Jr, Bartus RT, Siffert J, Davis CS, Lozano A, Boulis N, et al. Gene delivery of AAV2-neurturin for Parkinson’s disease: a double-blind, randomised, controlled trial. Lancet Neurol. 2010;9:1164–72.

Article  CAS  PubMed  Google Scholar 

Naso MF, Tomkowicz B, Perry WL 3rd, Strohl WR. Adeno-Associated Virus (AAV) as a Vector for Gene Therapy. BioDrugs. 2017;31:317–34.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nagahara AH, Wilson BR, Ivasyk I, Kovacs I, Rawalji S, Bringas JR, et al. MR-guided delivery of AAV2-BDNF into the entorhinal cortex of non-human primates. Gene Ther. 2018;25:104–14.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Christine CW, Bankiewicz KS, Van Laar AD, Richardson RM, Ravina B, Kells AP, et al. Magnetic resonance imaging-guided phase 1 trial of putaminal AADC gene therapy for Parkinson’s disease. Ann Neurol. 2019;85:704–14.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pearson TS, Gupta N, San Sebastian W, Imamura-Ching J, Viehoever A, Grijalvo-Perez A, et al. Gene therapy for aromatic L-amino acid decarboxylase deficiency by MR-guided direct delivery of AAV2-AADC to midbrain dopaminergic neurons. Nat Commun. 2021;12:4251.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Christine CW, Richardson RM, Van Laar AD, Thompson ME, Fine EM, Khwaja OS, et al. Safety of AADC Gene Therapy for moderately advanced parkinson disease: three-year outcomes from the PD-1101 Trial. Neurology. 2022;98:e40–e50.

Article  CAS  PubMed  Google Scholar 

Van Laar AD, Christine CW, Phielipp N, Larson PS, Elder JB, Merola A, et al. Intraputaminal Delivery of Adeno-Associated Virus Serotype 2-Glial Cell Line-Derived Neurotrophic Factor in Mild or Moderate Parkinson’s Disease. Mov Disord. 2025;40:1297–306.

Article  PubMed  PubMed Central  Google Scholar 

Koczot FJ, Carter BJ, Garon CF, Rose JA. Self-complementarity of terminal sequences within plus or minus strands of adenovirus-associated virus DNA. Proc Natl Acad Sci USA. 1973;70:215–9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Berns KI, Giraud C. Biology of adeno-associated virus. Curr Top Microbiol Immunol. 1996;218:1–23.

CAS  PubMed  Google Scholar 

Linden RM, Berns KI. Molecular biology of adeno-associated viruses. Contrib Microbiol. 2000;4:68–84.

Article  CAS  PubMed  Google Scholar 

Summerford C, Samulski RJ. Membrane-associated heparan sulfate proteoglycan is a receptor for adeno-associated virus type 2 virions. J Virol. 1998;72:1438–45.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Opie SR, Warrington KH Jr, Agbandje-McKenna M, Zolotukhin S, Muzyczka N. Identification of amino acid residues in the capsid proteins of adeno-associated virus type 2 that contribute to heparan sulfate proteoglycan binding. J Virol. 2003;77:6995–7006.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kern A, Schmidt K, Leder C, Müller OJ, Wobus CE, Bettinger K, et al. Identification of a heparin-binding motif on adeno-associated virus type 2 capsids. J Virol. 2003;77:11072–81.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Summerford C, Bartlett JS, Samulski RJ. AlphaVbeta5 integrin: a co-receptor for adeno-associated virus type 2 infection. Nat Med. 1999;5:78–82.

Article  CAS  PubMed  Google Scholar 

Pillay S, Meyer NL, Puschnik AS, Davulcu O, Diep J, Ishikawa Y, et al. An essential receptor for adeno-associated virus infection. Nature. 2016;530:108–12.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Summerford C, Johnson JS, Samulski RJ. AAVR: A Multi-Serotype Receptor for AAV. Mol Ther. 2016;24:663–6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pillay S, Carette JE. Host determinants of adeno-associated viral vector entry. Curr Opin Virol. 2017;24:124–31.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pillay S, Zou W, Cheng F, Puschnik AS, Meyer NL, Ganaie SS, et al. Adeno-associated Virus (AAV) Serotypes have distinctive interactions with domains of the cellular AAV receptor. J Virol. 2017;91. https://doi.org/10.1128/jvi.00391-17.

Nonnenmacher M, Weber T. Adeno-associated virus 2 infection requires endocytosis through the CLIC/GEEC pathway. Cell Host Microbe. 2011;10:563–76.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Girod A, Wobus CE, Zádori Z, Ried M, Leike K, Tijssen P, et al. The VP1 capsid protein of adeno-associated virus type 2 is carrying a phospholipase A2 domain required for virus infectivity. J Gen Virol. 2002;83:973–8.

Article  CAS  PubMed  Google Scholar 

Sonntag F, Bleker S, Leuchs B, Fischer R, Kleinschmidt JA. Adeno-associated virus type 2 capsids with externalized VP1/VP2 trafficking domains are generated prior to passage through the cytoplasm and are maintained until uncoating occurs in the nucleus. J Virol. 2006;80:11040–54.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Johnson JS, Samulski RJ. Enhancement of adeno-associated virus infection by mobilizing capsids into and out of the nucleolus. J Virol. 2009;83:2632–44.

Article  CAS  PubMed  Google Scholar 

Nonnenmacher M, Weber T. Intracellular transport of recombinant adeno-associated virus vectors. Gene Ther. 2012;19:649–58.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lux K, Goerlitz N, Schlemminger S, Perabo L, Goldnau D, Endell J, et al. Green fluorescent protein-tagged adeno-associated virus particles allow the study of cytosolic and nuclear trafficking. J Virol. 2005;79:11776–87.

Article  CAS  PubMed  PubMed Central 

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