Biomaterials at the interface of nano- and micro-scale vector–cellular interactions in genetic vaccine design

Jones, Charles H.; Håkansson, Anders P.; Pfeifer, Blaine A.

doi:10.1039/c4tb01058b

Cited by 10 publications

(13 citation statements)

References 182 publications

(267 reference statements)

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“…In this sense, the costs to develop non-viral gene delivery vectors is clearly marginal if compared with viral counterparts, since mass production of viral vectors requires the development of expensive scalable and robust processes that affect, for instance, the studies on cell cultures or the amplification and purification steps. [ 111 ]. However, although being more affordable from an economical point of view, to reach clinical practice, non-viral vectors require multiple rounds of engineering and many chemical modifications, including the addition of stabilizing components or bioactive targeting ligands that increase their complexity and, therefore, the price of the formulations [ 105 ].…”

Section: Commercialization Processmentioning

confidence: 99%

How Far Are Non-Viral Vectors to Come of Age and Reach Clinical Translation in Gene Therapy?

Sainz-Ramos

Gallego

Villate-Beitia

et al. 2021

IJMS

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Efficient delivery of genetic material into cells is a critical process to translate gene therapy into clinical practice. In this sense, the increased knowledge acquired during past years in the molecular biology and nanotechnology fields has contributed to the development of different kinds of non-viral vector systems as a promising alternative to virus-based gene delivery counterparts. Consequently, the development of non-viral vectors has gained attention, and nowadays, gene delivery mediated by these systems is considered as the cornerstone of modern gene therapy due to relevant advantages such as low toxicity, poor immunogenicity and high packing capacity. However, despite these relevant advantages, non-viral vectors have been poorly translated into clinical success. This review addresses some critical issues that need to be considered for clinical practice application of non-viral vectors in mainstream medicine, such as efficiency, biocompatibility, long-lasting effect, route of administration, design of experimental condition or commercialization process. In addition, potential strategies for overcoming main hurdles are also addressed. Overall, this review aims to raise awareness among the scientific community and help researchers gain knowledge in the design of safe and efficient non-viral gene delivery systems for clinical applications to progress in the gene therapy field.

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Section: Commercialization Processmentioning

confidence: 99%

How Far Are Non-Viral Vectors to Come of Age and Reach Clinical Translation in Gene Therapy?

Sainz-Ramos

Gallego

Villate-Beitia

et al. 2021

IJMS

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“…Due to properties such as negative charge or large size, most biomacromolecules require vectors for delivery [1]. Over the last twenty years, the number of clinical trials evaluating gene-delivery technology has steadily increased [2], but these trials have only yielded five products globally, and none in the United States [3]. These products, none of which were approved prior to 2003, include: Gendicine, Oncorine, Rexin G, Neovasculgen, and Glybera.…”

Section: Gene Therapy Technology and Limitationsmentioning

confidence: 99%

“…Successful clinical development requires that sufficient gene delivery performance is achieved without incurring expensive synthetic schemes. Interestingly, even when a particular nonviral vector requires an expensive synthesis scheme, the cost is marginal when compared to viral alternatives [3]. More specifically, the development of robust and scalable processes for mass production of viral vectors (which include labor- intensive cell culture and purification steps) remains an economic challenge that impedes potential therapeutic use [112].…”

Section: Manufacturing Considerationsmentioning

confidence: 99%

Overcoming Gene-Delivery Hurdles: Physiological Considerations for Nonviral Vectors

Hill

Chen

et al. 2016

Trends in Biotechnology

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145

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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. This review evaluates potential avenues towards improving the transition of gene delivery technologies from in vitro assessment to human clinical therapy.

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“…Of these, genetic vaccines are ideal candidates, as this vaccine variation offers the most flexibility in terms of antigen design, production, and storage potential [1]. Furthermore, genetic vaccines are predicated on the controlled introduction of genetic material into immune effector cells for the eventual induction of an adaptive immune response [2].…”

Section: Introductionmentioning

confidence: 99%

Influence of molecular weight upon mannosylated bio-synthetic hybrids for targeted antigen presenting cell gene delivery

et al. 2015

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Given the rise of antibiotic resistant microbes, genetic vaccination is a promising prophylactic strategy that enables rapid design and manufacture. Facilitating this process is the choice of vector, which is often situationally-specific and limited in engineering capacity. Furthermore, these shortcomings are usually tied to an incomplete understanding of the structure-function relationships driving vector-mediated gene delivery. Building upon our initial report of a hybrid bacterial-biomaterial gene delivery vector, a comprehensive structure-function assessment was completed using a class of mannosylated poly(beta-amino esters). Through a top-down screening methodology, an ideal polymer was selected on the basis of gene delivery efficacy and then used for the synthesis of a stratified molecular weight polymer library. By eliminating contributions of polymer chemical background, we were able to complete an in-depth assessment of gene delivery as a function of (1) polymer molecular weight, (2) relative mannose content, (3) polymer-membrane biophysical properties, (4) APC uptake specificity, and (5) serum inhibition. In summary, the flexibility and potential of the hybrid design featured in this work highlights the ability to systematically probe vector-associated properties for the development of translational gene delivery candidates.

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Biomaterials at the interface of nano- and micro-scale vector–cellular interactions in genetic vaccine design

Cited by 10 publications

References 182 publications

How Far Are Non-Viral Vectors to Come of Age and Reach Clinical Translation in Gene Therapy?

How Far Are Non-Viral Vectors to Come of Age and Reach Clinical Translation in Gene Therapy?

Overcoming Gene-Delivery Hurdles: Physiological Considerations for Nonviral Vectors

Influence of molecular weight upon mannosylated bio-synthetic hybrids for targeted antigen presenting cell gene delivery

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