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Molecular conjugates are nanometer-sized entities consisting of synthetic materials (lipids, polycations, targeting agents, and so on) and nucleic acids. These composites are delivery vehicles that function to provide the transport of nucleic acids to sites of action. Recently, great progress has been made in the construction of these nonviral delivery vehicles and the understanding of how they function...
In the late 1980s, Vical and collaborators discovered that the injection into tissues of unformulated plasmid encoding various proteins resulted in the uptake of the plasmid by cells and expression of the encoded proteins. After this discovery, a period of technological improvements in plasmid delivery and expression and in pharmaceutical and manufacturing development was quickly followed by a plethora...
The potential use of genetic vaccines to address numerous diseases including cancer is promising, but currently unrealized. Here, we review advances in the nonviral delivery of antigen-encoded plasmid DNA for the purpose of treating cancer through the human immune system, as this disease has drawn the most attention in this field to date. Brief overviews of dendritic cell immunobiology and the mechanism...
Adeno-associated virus (AAV) has emerged as an attractive vector for gene therapy. AAV vectors have successfully been utilized to promote sustained gene expression in a variety of tissues such as muscle, eye, brain, liver, and lung [1,2,3,4, 5,6,7]. As the significance of AAV as a gene therapy vector has been realized over the past years, recent developments in recombinant AAV (rAAV) production and...
Targeted gene delivery involves broadening viral tropism to infect previously nonpermissive cells, replacing viral tropism to infect a target cell exclusively, or stealthing the vector against nonspecific interactions with host cells and proteins. These approaches offer the potential advantages of enhanced therapeutic effects, reduced side effects, lowered dosages, and enhanced therapeutic economics...
We review the use of lentiviral vectors in current human gene therapy applications that involve genetic modification of nondividing tissues with integrated transgenes. Safety issues, including insertional mutagenesis and replication-competent retroviruses, are discussed. Innate cellular defenses against retroviruses and their implications for human gene therapy with different lentiviral vectors are...
Adenovirus vectors have attracted considerable interest over the past decade, with ongoing clinical development programs for applications ranging from replacement therapy for protein deficiencies to cancer therapeutics to prophylactic vaccines. Consequently, considerable product, process, analytical, and formulation development has been undertaken to support these programs. For example, “gutless”...
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