Dataset Information

Overcoming Gene-Delivery Hurdles: Physiological Considerations for Nonviral Vectors.

ABSTRACT: With the use of contemporary tools and techniques, it has become possible to more precisely tune the biochemical mechanisms associated with using nonviral vectors for gene delivery. Consequently, nonviral vectors can incorporate numerous vector compositions and types of genetic cargo to develop diverse genetic therapies. Despite these advantages, gene-delivery strategies using nonviral vectors have poorly translated into clinical success due to preclinical experimental design considerations that inadequately predict therapeutic efficacy. Furthermore, the manufacturing and distribution processes are critical considerations for clinical application that should be considered when developing therapeutic platforms. In this review, we evaluate potential avenues towards improving the transition of gene-delivery technologies from in vitro assessment to human clinical therapy.

SUBMITTER: Hill AB

PROVIDER: S-EPMC5800990 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Overcoming Gene-Delivery Hurdles: Physiological Considerations for Nonviral Vectors.

Hill Andrew B AB Chen Mingfu M Chen Chih-Kuang CK Pfeifer Blaine A BA Jones Charles H CH

Trends in biotechnology 20151223 2

With the use of contemporary tools and techniques, it has become possible to more precisely tune the biochemical mechanisms associated with using nonviral vectors for gene delivery. Consequently, nonviral vectors can incorporate numerous vector compositions and types of genetic cargo to develop diverse genetic therapies. Despite these advantages, gene-delivery strategies using nonviral vectors have poorly translated into clinical success due to preclinical experimental design considerations that ...[more]

PMID: 26727153

Similar Datasets

Project description:A new class of water-soluble C60 transfecting agents has been prepared using Hirsch-Bingel chemistry and assessed for their ability to act as gene-delivery vectors in vitro. In an effort to elucidate the relationship between the hydrophobicity of the fullerene core, the hydrophilicity of the water-solubilizing groups, and the overall charge state of the C60 vectors in gene delivery and expression, several different C60 derivatives were synthesized to yield either positively charged, negatively charged, or neutral chemical functionalities under physiological conditions. These fullerene derivatives were then tested for their ability to transfect cells grown in culture with DNA carrying the green fluorescent protein (GFP) reporter gene. Statistically significant expression of GFP was observed for all forms of the C60 derivatives when used as DNA vectors and compared to the ability of naked DNA alone to transfect cells. However, efficient in vitro transfection was only achieved with the two positively charged C60 derivatives, namely, an octa-amino derivatized C60 and a dodeca-amino derivatized C60 vector. All C60 vectors showed an increase in toxicity in a dose-dependent manner. Increased levels of cellular toxicity were observed for positively charged C60 vectors relative to the negatively charged and neutral vectors. Structural analyses using dynamic light scattering and optical microscopy offered further insights into possible correlations between the various derivatized C60 compounds, the C60 vector/DNA complexes, their physical attributes (aggregation, charge) and their transfection efficiencies. Recently, similar Gd@C60-based compounds have demonstrated potential as advanced contrast agents for magnetic resonance imaging (MRI). Thus, the successful demonstration of intracellular DNA uptake, intracellular transport, and gene expression from DNA using C60 vectors suggests the possibility of developing analogous Gd@C60-based vectors to serve simultaneously as both therapeutic and diagnostic agents.

Dataset Information

Overcoming Gene-Delivery Hurdles: Physiological Considerations for Nonviral Vectors.

Publications

Overcoming Gene-Delivery Hurdles: Physiological Considerations for Nonviral Vectors.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets