Journal ArticleDOI
New recombinant serotypes of AAV vectors.
TLDR
Initial evaluation in mouse models of vectors based on these novel AAVs for tissue tropism and gene transfer potency led to the identification of some vector with improved gene transfer to different target tissues.Abstract:
AAV based vectors can achieve stable gene transfer with minimal vector related toxicities. AAV serotype 2 (AAV2) is the first AAV that was vectored for gene transfer applications. However, the restricted tissue tropism of AAV and its low transduction efficiency have limited its further development as vector. Recent studies using vectors derived from alternative AAV serotypes such as AAV1, 4, 5 and 6 have shown improved potency and broadened tropism of the AAV vector by packaging the same vector genome with different AAV capsids. In an attempt to search for potent AAV vectors with enhanced performance profiles, molecular techniques were employed for the detection and isolation of endogenous AAVs from a variety of human and non-human primate (NHP) tissues. A family of novel primate AAVs consisting of 110 non-redundant species of proviral sequences was discovered and turned to be prevalent in 18-19% of the tissues evaluated. Phylogenetic and functional analyses revealed that primate AAVs are segregated into clades based on phylogenetic relatedness. The members within a clade share functional and serological properties. Initial evaluation in mouse models of vectors based on these novel AAVs for tissue tropism and gene transfer potency led to the identification of some vector with improved gene transfer to different target tissues. Gene therapy treatment of several mouse and canine models with novel AAV vectors achieved long term phenotypic corrections. Vectors based on new primate AAVs could become the next generation of efficient gene transfer vehicles for various gene therapy applications.read more
Citations
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In vivo genome editing using Staphylococcus aureus Cas9
F. Ann Ran,Le Cong,Winston X. Yan,David A. Scott,Jonathan S. Gootenberg,Andrea J. Kriz,Bernd Zetsche,Ophir Shalem,Xuebing Wu,Kira S. Makarova,Eugene V. Koonin,Phillip A. Sharp,Feng Zhang +12 more
TL;DR: In this paper, the RNA-guided endonuclease Cas9 has emerged as a versatile genome-editing platform and has been used for basic research and therapeutic applications that use the highly versatile adeno-associated virus (AAV) delivery vehicle.
Journal ArticleDOI
In vivo genome editing using Staphylococcus aureus Cas9
F. Ann Ran,Le Cong,Winston X. Yan,David A. Scott,Jonathan S. Gootenberg,Andrea J. Kriz,Bernd Zetsche,Ophir Shalem,Xuebing Wu,Kira S. Makarova,Eugene V. Koonin,Phillip A. Sharp,Feng Zhang +12 more
TL;DR: Six smaller Cas9 orthologues are characterized and it is shown that Cas9 from Staphylococcus aureus (SaCas9) can edit the genome with efficiencies similar to those of SpCas9, while being more than 1 kilobase shorter.
Journal ArticleDOI
Gene Therapy Using Adeno-Associated Virus Vectors
Shyam Daya,Kenneth I. Berns +1 more
TL;DR: Several novel approaches and recent findings that promise to expand AAV's utility are discussed, especially in the context of combining gene therapy ex vivo with new advances in stem or progenitor cell biology.
Journal ArticleDOI
Adeno-associated virus serotypes: vector toolkit for human gene therapy.
TL;DR: This review is focused on recent developments in the isolation of novel AAV serotypes and isolates, their production and purification, diverse tissue tropisms, mechanisms of cellular entry/trafficking, and capsid structure.
Journal ArticleDOI
Prevalence of serum IgG and neutralizing factors against adeno-associated virus (AAV) types 1, 2, 5, 6, 8, and 9 in the healthy population: implications for gene therapy using AAV vectors.
Sylvie Boutin,Virginie Monteilhet,Philippe Veron,Christian Leborgne,Olivier Benveniste,Marie Montus,Carole Masurier +6 more
TL;DR: Characterization of the preexisting humoral responses to the AAV capsid and cross-reactivity will allow development of new strategies to circumvent AAV acquired immune responses, and vectors based on AAV5, AAV8, and AAV9 may have an advantage for gene therapy in humans.
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