Workshop on Long-term Follow-up of Participants in Human Gene Transfer Research

Nyberg, Kara A.; Carter, Barrie J.; Chen, Theresa; Dunbar, Cynthia E.; Flotte, TR; Rose, Steven; Rosenblum, Daniel; Simek, Stephanie L.; Wilson, C. Ruth

doi:10.1016/j.ymthe.2004.10.011

Cited by 21 publications

(6 citation statements)

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“…[30][31][32][33][34] Taken together, our results suggest a highly novel approach to chronic treatment of AMD in humans using the well-characterized, nonintegrating, and well-tolerated adenovirus vector to deliver antiangiogenic genes. [35][36][37] These studies show that repeat protein delivery is possible following a single intraocular injection to the eye. Moreover, this promising technical innovation may be translatable as well to other applications for the treatment of chronic diseases.…”

Section: Discussionmentioning

confidence: 99%

Repeat Administration of Proteins to the Eye With a Single Intraocular Injection of an Adenovirus Vector

et al. 2008

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Delivery of therapeutic proteins, such as antiangiogenic proteins, to the eye is a demonstrated method for the control of age-related macular degeneration (AMD). However, one of the key limitations is the requirement for frequent and repeated intraocular injections. In this article, we demonstrate that repeated protein production in the eye can be stimulated from the cytomegalovirus (CMV) promoter without repeat intraocular injections using a small molecule, all-trans retinoic acid (ATRA). ATRA by systemic delivery can stimulate protein production multiple times in the eye. Administration of ATRA resulted in stimulation of gene expression to relevant levels that block abnormal blood vessel growth in an experimental animal model for AMD. These data support the principles of this technological discovery to therapeutic applications for chronic ocular diseases.

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Section: Discussionmentioning

confidence: 99%

Repeat Administration of Proteins to the Eye With a Single Intraocular Injection of an Adenovirus Vector

et al. 2008

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“…Instead, the FDA's Center for Biologics Evaluation and Research (CBER) has compiled a set of guidelines for long-term follow-up of patients enrolled in human gene transfer studies (www.asgt.org/ regulatoryissues.shtml). These guidelines were born out of a workshop on long-term follow-up of patients at the 2004 Meeting of the American Society of Gene Therapy (ASGT) in which the potential long-term risks were recognized as ''...persistence of vector sequences, integration of the vector into host genomic DNA, and transgene-specific effects'' [155]. CBER guidelines to test vector stocks for RCLs can also be acquired through the indicated website.…”

Section: Biosafety Standards and Assaysmentioning

confidence: 99%

Gene delivery by lentivirus vectors

2007

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The capacity to efficiently transduce nondividing cells, shuttle large genetic payloads, and maintain stable long-term transgene expression are attributes that have brought lentiviral vectors to the forefront of gene delivery vehicles for research and therapeutic applications in a clinical setting. Our discussion initiates with advances in lentiviral vector development and how these sophisticated lentiviral vectors reflect improvements in safety, regarding the prevention of replication competent lentiviruses (RCLs), vector mobilization, and insertional mutagenesis. Additionally, we describe conventional molecular regulatory systems to manage gene expression levels in a spatial and temporal fashion in the context of a lentiviral vector. State of the art technology for lentiviral vector production by transient transfection and packaging cell lines are explicitly presented with current practices used for concentration, purification, titering, and determining the safety of a vector stock. We summarize lentiviral vector applications that have received a great deal of attention in recent years including the generation of transgenic animals and the stable delivery of RNA interference molecules. Concluding remarks address some of the successes in preclinical animals, and the recent transition of lentiviral vectors to human clinical trials as therapy for a variety of infectious and genetic diseases.

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“…(Suter et al, 2004). Additionally, since the dog leukocyte antigen type I and II loci are fully characterized, this provides the opportunity to evaluate gene-therapy based approaches in an allogeneic transplantation setting (Ladiges et al, 1990;Maris & Storb, 2002;Nyberg et al, 2004;Suter et al, 2004;Venkataraman et al, 2007;Wagner et al, 1999). Due to the clinical applicability of the results obtained in the dog model, a large amount of effort has been devoted to optimizing the conditions in the dog model which include optimizing the procedures to mobilize HSCs, culture these cells ex vivo, as well as transduce them with retroviral vectors and achieve efficient engraftment in vivo (Goerner et al, 1999;Goerner et al, 2001;Horn et al, 2004a;Kiem et al, 2007;Kiem et al, 1996a;Kiem et al, 1999).…”

Section: In Vivo Selection Of Chemoresistant Hspcs In Large Animal Momentioning

confidence: 99%