How will the field of gene therapy survive its success?

Kaemmerer, William F.

doi:10.1002/btm2.10090

Cited by 36 publications

(19 citation statements)

References 58 publications

(96 reference statements)

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“…When designing circRNA therapeutics, there are some important issues to be considered, most of which are in common with all gene-based therapies [ 87 ].…”

Section: Therapeutic Perspectives Of Circrnasmentioning

confidence: 99%

Circular RNAs in Muscle Function and Disease

Greco

Cardinali

Falcone

et al. 2018

IJMS

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Circular RNAs (circRNAs) are a class of RNA produced during pre-mRNA splicing that are emerging as new members of the gene regulatory network. In addition to being spliced in a linear fashion, exons of pre-mRNAs can be circularized by use of the 3′ acceptor splice site of upstream exons, leading to the formation of circular RNA species. In this way, genetic information can be re-organized, increasing gene expression potential. Expression of circRNAs is developmentally regulated, tissue and cell-type specific, and shared across eukaryotes. The importance of circRNAs in gene regulation is now beginning to be recognized and some putative functions have been assigned to them, such as the sequestration of microRNAs or proteins, the modulation of transcription, the interference with splicing, and translation of small proteins. In accordance with an important role in normal cell biology, circRNA deregulation has been reported to be associated with diseases. Recent evidence demonstrated that circRNAs are highly expressed in striated muscle tissue, both skeletal and cardiac, that is also one of the body tissue showing the highest levels of alternative splicing. Moreover, initial studies revealed altered circRNA expression in diseases involving striated muscle, suggesting important functions of these molecules in the pathogenetic mechanisms of both heart and skeletal muscle diseases. The recent findings in this field will be described and discussed.

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“…When designing circRNA therapeutics, there are some important issues to be considered, most of which are in common with all gene-based therapies [ 87 ].…”

Section: Therapeutic Perspectives Of Circrnasmentioning

confidence: 99%

Circular RNAs in Muscle Function and Disease

Greco

Cardinali

Falcone

et al. 2018

IJMS

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“…Ever increasing demands for vaccination and gene therapy have raised the need to develop efficient large-scale manufacturing processes, including cell culture-based virus production (Kaemmerer 2018;Rappuoli and Hanon 2018). One option for intensified, rapid, and flexible biological manufacturing is high cell density perfusion cultures (Bielser et al 2018;Chen et al 2018).…”

Section: Introductionmentioning

confidence: 99%

Performance of an acoustic settler versus a hollow fiber–based ATF technology for influenza virus production in perfusion

Gränicher

Coronel

Trampler³

et al. 2020

Appl Microbiol Biotechnol

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Process intensification and integration is crucial regarding an ever increasing pressure on manufacturing costs and capacities in biologics manufacturing. For virus production in perfusion mode, membrane-based alternating tangential flow filtration (ATF) and acoustic settler are the commonly described cell retention technologies. While acoustic settlers allow for continuous influenza virus harvesting, the use of commercially available membranes for ATF systems typically results in the accumulation of virus particles in the bioreactor vessel. Accordingly, with one single harvest at the end of a cultivation, this increases the risk of lowering the product quality. To assess which cell retention device would be most suitable for influenza A virus production, we compared various key performance figures using AGE1.CR.pIX cells at concentrations between 25 and 50 × 10 6 cells/mL at similar infection conditions using either an ATF system or an acoustic settler. Production yields, process-related impurities, and aggregation of viruses and other large molecules were evaluated. Taking into account the total number of virions from both the bioreactor and the harvest vessel, a 1.5-3.0-fold higher volumetric virus yield was obtained for the acoustic settler. In addition, fewer large-sized aggregates (virus particles and other molecules) were observed in the harvest taken directly from the bioreactor. In contrast, similar levels of process-related impurities (host cell dsDNA, total protein) were obtained in the harvest for both retention systems. Overall, a clear advantage was observed for continuous virus harvesting after the acoustic settler operation mode was optimized. This development may also allow direct integration of subsequent downstream processing steps. Key points• High suspension cell density, immortalized avian cell line, influenza vaccine.

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“…However, there are multiple hurdles for AAV-based gene therapy to achieve its full potential. (1) Low transduction efficiency, (2) pre-existing nAb against AAVs, (3) transgene toxicity and loss of expression, and (4) extremely high price tag (Colella et al, 2018;Kaemmerer, 2018). Fortunately, multiple strategies have been developed to address these hurdles (Tse et al, 2015).…”

Section: The Challengesmentioning

confidence: 99%

The Current and Future State of Vaccines, Antivirals and Gene Therapies Against Emerging Coronaviruses

et al. 2020

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Emerging coronaviruses (CoV) are constant global public health threats to society. Multiple ongoing clinical trials for vaccines and antivirals against CoVs showcase the availability of medical interventions to both prevent and treat the future emergence of highly pathogenic CoVs in human. However, given the diverse nature of CoVs and our close interactions with wild, domestic and companion animals, the next epidemic zoonotic CoV could resist the existing vaccines and antivirals developed, which are primarily focused on Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS CoV). In late 2019, the novel CoV (SARS-CoV-2) emerged in Wuhan, China, causing global public health concern. In this review, we will summarize the key advancements of current vaccines and antivirals against SARS-CoV and MERS-CoV as well as discuss the challenge and opportunity in the current SARS-CoV-2 crisis. At the end, we advocate the development of a "plug-and-play" platform technologies that could allow quick manufacturing and administration of broad-spectrum countermeasures in an outbreak setting. We will discuss the potential of AAV-based gene therapy technology for in vivo therapeutic antibody delivery to combat SARS-CoV-2 outbreak and the future emergence of severe CoVs.

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How will the field of gene therapy survive its success?

Cited by 36 publications

References 58 publications

Circular RNAs in Muscle Function and Disease

Circular RNAs in Muscle Function and Disease

Performance of an acoustic settler versus a hollow fiber–based ATF technology for influenza virus production in perfusion

The Current and Future State of Vaccines, Antivirals and Gene Therapies Against Emerging Coronaviruses

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