Emerging Issues in AAV-Mediated In Vivo Gene Therapy
TLDR
The liver will be used as a model target tissue for gene transfer based on the large amount of data available from preclinical and clinical studies, and key achievements and emerging issues in the field are presented.Abstract:
In recent years, the number of clinical trials in which adeno-associated virus (AAV) vectors have been used for in vivo gene transfer has steadily increased. The excellent safety profile, together with the high efficiency of transduction of a broad range of target tissues, has established AAV vectors as the platform of choice for in vivo gene therapy. Successful application of the AAV technology has also been achieved in the clinic for a variety of conditions, including coagulation disorders, inherited blindness, and neurodegenerative diseases, among others. Clinical translation of novel and effective "therapeutic products" is, however, a long process that involves several cycles of iterations from bench to bedside that are required to address issues encountered during drug development. For the AAV vector gene transfer technology, several hurdles have emerged in both preclinical studies and clinical trials; addressing these issues will allow in the future to expand the scope of AAV gene transfer as a therapeutic modality for a variety of human diseases. In this review, we will give an overview on the biology of AAV vector, discuss the design of AAV-based gene therapy strategies for in vivo applications, and present key achievements and emerging issues in the field. We will use the liver as a model target tissue for gene transfer based on the large amount of data available from preclinical and clinical studies.read more
Citations
More filters
Journal ArticleDOI
Adeno-associated virus vector as a platform for gene therapy delivery
TL;DR: The fundamentals of AAV and vectorology are discussed, focusing on current therapeutic strategies, clinical progress and ongoing challenges.
Journal ArticleDOI
Immune Responses to Viral Gene Therapy Vectors.
TL;DR: This review provides an overview of the type of immune responses that have been documented in animal models and in humans who received gene transfer with one of three widely tested vector systems, namely adenoviral, lentiviral, or adeno-associated viral vectors.
Journal ArticleDOI
AAV Vector Immunogenicity in Humans: A Long Journey to Successful Gene Transfer
TL;DR: Data emerging from clinical trials across a broad range of gene therapy applications is reviewed, suggesting common features of immune responses to AAV can be found, suggesting that vector immunogenicity is dose-dependent, and that innate immunity plays an important role in the outcome of gene transfer.
Journal ArticleDOI
CRISPR-Based Therapeutic Genome Editing: Strategies and In Vivo Delivery by AAV Vectors.
TL;DR: CRISPR-based strategies to improve human health, with an emphasis on the delivery of CRISPR therapeutics directly into the human body using adeno-associated virus (AAV) vectors are described.
Journal ArticleDOI
MicroRNA delivery through nanoparticles.
Sharon Wei Ling Lee,Camilla Paoletti,Marco Campisi,Tatsuya Osaki,Tatsuya Osaki,Giulia Adriani,Giulia Adriani,Roger D. Kamm,Roger D. Kamm,Clara Mattu,Valeria Chiono +10 more
TL;DR: This review critically discusses the use of nanoparticles for the delivery of miRNA-based therapeutics in the treatment of cancer and neurodegenerative disorders and for tissue regeneration.
References
More filters
Journal ArticleDOI
Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response
Catherine S. Manno,Glenn F. Pierce,Valder R. Arruda,Bertil Glader,Margaret V. Ragni,Rasko Jj,Margareth C. Ozelo,Keith Hoots,Blatt P,Barbara A. Konkle,Michael D. Dake,Robin D. Kaye,Mahmood K. Razavi,A Zajko,James L. Zehnder,Pradip Rustagi,Hiroyuki Nakai,A Chew,Debra G.B. Leonard,Debra G.B. Leonard,J F Wright,Ruth Lessard,Jurg M. Sommer,Michael Tigges,Denise E. Sabatino,A Luk,Haiyan Jiang,Federico Mingozzi,Linda B. Couto,Hildegund C.J. Ertl,Katherine A. High,Katherine A. High,Mark A. Kay +32 more
TL;DR: In this article, a single portal vein infusion of a recombinant adeno-associated viral vector (rAAV) expressing canine Factor IX (F.IX) resulted in long-term expression of therapeutic levels of F.IX in dogs with severe hemophilia B.
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
Adenovirus-Associated Virus Vector–Mediated Gene Transfer in Hemophilia B
Amit C. Nathwani,Edward G. D. Tuddenham,Savita Rangarajan,Cecilia Rosales,Jenny McIntosh,David C. Linch,Pratima Chowdary,Anne Riddell,Arnulfo Jaquilmac Pie,Chris Harrington,James O'Beirne,Keith Smith,John Pasi,Bertil Glader,Pradip Rustagi,Catherine Y.C. Ng,Mark A. Kay,Junfang Zhou,Yunyu Spence,Christopher L. Morton,James A. Allay,John Coleman,Susan Sleep,John M. Cunningham,Deokumar Srivastava,Etiena Basner-Tschakarjan,Federico Mingozzi,Katherine A. High,John T. Gray,Ulrike M. Reiss,Arthur W. Nienhuis,Andrew M. Davidoff +31 more
TL;DR: Peripheral-vein infusion of scAAV2/8-LP1-hFIXco resulted in FIX transgene expression at levels sufficient to improve the bleeding phenotype, with few side effects.
Journal ArticleDOI
Novel adeno-associated viruses from rhesus monkeys as vectors for human gene therapy
TL;DR: Vectors based on AAV7 and AAV8 should be considered for human gene therapy because of low reactivity to antibodies directed to human AAVs and because gene transfer efficiency in muscle was similar to that obtained with the best known serotype, whereas, in liver, gene transfer was substantially higher than previously described.
Related Papers (5)
Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy
Jerry R. Mendell,Samiah Al-Zaidy,Richard Shell,W. Dave Arnold,Louise R. Rodino-Klapac,Thomas W. Prior,Linda Lowes,Lindsay N. Alfano,K. Berry,Kathleen Church,John T. Kissel,Sukumar Nagendran,James L’Italien,Douglas M. Sproule,Courtney Wells,Jessica A. Cardenas,Marjet D. Heitzer,Allan Arman Kaspar,Sarah Corcoran,Lyndsey Braun,Shibi Likhite,Carlos Henrique Miranda,Kathrin Meyer,K.D. Foust,Arthur H.M. Burghes,Brian K. Kaspar +25 more
Long-term safety and efficacy of factor IX gene therapy in hemophilia B
Amit C. Nathwani,Ulreke M Reiss,Edward G. D. Tuddenham,Cecilia Rosales,Cecilia Rosales,Pratima Chowdary,Jenny McIntosh,Marco Della Peruta,Elsa Lheriteau,Nishal Patel,Deepak Raj,Deepak Raj,Anne Riddell,Jun Pie,Savita Rangarajan,Savita Rangarajan,David H. Bevan,Michael Recht,Yu-min P Shen,Kathleen Halka,Etiena Basner-Tschakarjan,Federico Mingozzi,Katherine A. High,James A. Allay,Mark A. Kay,Catherine Y.C. Ng,Junfang Zhou,Maria I Cancio,Christopher L. Morton,John T. Gray,Deo Kumar Srivastava,Arthur W. Nienhuis,Andrew M. Davidoff +32 more
Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response
Catherine S. Manno,Glenn F. Pierce,Valder R. Arruda,Bertil Glader,Margaret V. Ragni,Rasko Jj,Margareth C. Ozelo,Keith Hoots,Blatt P,Barbara A. Konkle,Michael D. Dake,Robin D. Kaye,Mahmood K. Razavi,A Zajko,James L. Zehnder,Pradip Rustagi,Hiroyuki Nakai,A Chew,Debra G.B. Leonard,Debra G.B. Leonard,J F Wright,Ruth Lessard,Jurg M. Sommer,Michael Tigges,Denise E. Sabatino,A Luk,Haiyan Jiang,Federico Mingozzi,Linda B. Couto,Hildegund C.J. Ertl,Katherine A. High,Katherine A. High,Mark A. Kay +32 more
Adenovirus-Associated Virus Vector–Mediated Gene Transfer in Hemophilia B
Amit C. Nathwani,Edward G. D. Tuddenham,Savita Rangarajan,Cecilia Rosales,Jenny McIntosh,David C. Linch,Pratima Chowdary,Anne Riddell,Arnulfo Jaquilmac Pie,Chris Harrington,James O'Beirne,Keith Smith,John Pasi,Bertil Glader,Pradip Rustagi,Catherine Y.C. Ng,Mark A. Kay,Junfang Zhou,Yunyu Spence,Christopher L. Morton,James A. Allay,John Coleman,Susan Sleep,John M. Cunningham,Deokumar Srivastava,Etiena Basner-Tschakarjan,Federico Mingozzi,Katherine A. High,John T. Gray,Ulrike M. Reiss,Arthur W. Nienhuis,Andrew M. Davidoff +31 more