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The use of adenoviral vectors in gene therapy and vaccine approaches.

ABSTRACT: Adenovirus was first identified in the 1950s and since then this pathogenic group of viruses has been explored and transformed into a genetic transfer vehicle. Modification or deletion of few genes are necessary to transform it into a conditionally or non-replicative vector, creating a versatile tool capable of transducing different tissues and inducing high levels of transgene expression. In the early years of vector development, the application in monogenic diseases faced several hurdles, including short-term gene expression and even a fatality. On the other hand, an adenoviral delivery strategy for treatment of cancer was the first approved gene therapy product. There is an increasing interest in expressing transgenes with therapeutic potential targeting the cancer hallmarks, inhibiting metastasis, inducing cancer cell death or modulating the immune system to attack the tumor cells. Replicative adenovirus as vaccines may be even older and date to a few years of its discovery, application of non-replicative adenovirus for vaccination against different microorganisms has been investigated, but only recently, it demonstrated its full potential being one of the leading vaccination tools for COVID-19. This is not a new vector nor a new technology, but the result of decades of careful and intense work in this field.

SUBMITTER: Araujo NM

PROVIDER: S-EPMC9543183 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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The use of adenoviral vectors in gene therapy and vaccine approaches.

Araújo Natália Meneses NM Rubio Ileana Gabriela Sanchez IGS Toneto Nicholas Pietro Agulha NPA Morale Mirian Galliote MG Tamura Rodrigo Esaki RE

Genetics and molecular biology 20221007 3 Suppl 1

Adenovirus was first identified in the 1950s and since then this pathogenic group of viruses has been explored and transformed into a genetic transfer vehicle. Modification or deletion of few genes are necessary to transform it into a conditionally or non-replicative vector, creating a versatile tool capable of transducing different tissues and inducing high levels of transgene expression. In the early years of vector development, the application in monogenic diseases faced several hurdles, incl ...[more]

PMID: 36206378

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Project description:Despite the development of novel pharmacological treatments, cardiovascular disease morbidity and mortality remain high indicating an unmet clinical need. Viral gene therapy enables targeted delivery of therapeutic transgenes and represents an attractive platform for tackling acquired and inherited cardiovascular diseases in the future. Current cardiovascular gene therapy trials in humans mainly focus on improving cardiac angiogenesis and function. Encouragingly, local delivery of therapeutic transgenes utilising first-generation human adenovirus serotype (HAd)-5 is safe in the short term and has shown some efficacy in drug refractory angina pectoris and heart failure with reduced ejection fraction. Despite this success, systemic delivery of therapeutic HAd-5 vectors targeting cardiovascular tissues and internal organs is limited by negligible gene transfer to target cells, elimination by the immune system, liver sequestration, off-target effects, and episomal degradation. To circumvent these barriers, cardiovascular gene therapy research has focused on determining the safety and efficacy of rare alternative serotypes and/or genetically engineered adenoviral capsid protein-modified vectors following local or systemic delivery. Pre-clinical studies have identified several vectors including HAd-11, HAd-35, and HAd-20-42-42 as promising platforms for local and systemic targeting of vascular endothelial and smooth muscle cells. In the past, clinical gene therapy trials were often restricted by limited scale-up capabilities of gene therapy medicinal products (GTMPs) and lack of regulatory guidance. However, significant improvement of industrial GTMP scale-up and purification, development of novel producer cell lines, and issuing of GTMP regulatory guidance by national regulatory health agencies have addressed many of these challenges, creating a more robust framework for future adenoviral-based cardiovascular gene therapy. In addition, this has enabled the mass roll out of adenovirus vector-based COVID-19 vaccines. KEY MESSAGES: First-generation HAd-5 vectors are widely used in cardiovascular gene therapy. HAd-5-based gene therapy was shown to lead to cardiac angiogenesis and improved function. Novel HAd vectors may represent promising transgene carriers for systemic delivery. Novel methods allow industrial scale-up of rare/genetically altered Ad serotypes. National regulatory health agencies have issued guidance on GMP for GTMPs.

Dataset Information

The use of adenoviral vectors in gene therapy and vaccine approaches.

Publications

The use of adenoviral vectors in gene therapy and vaccine approaches.

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