Viruses as tools in gene therapy, vaccine development, and cancer treatment

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Using viruses to our advantage has been a huge leap for humanity. Their ability to mediate horizontal gene transfer has made them useful tools for gene therapy, vaccine development, and cancer treatment. Adenoviruses, adeno-associated viruses, retroviruses, lentiviruses, alphaviruses, and herpesviruses are a few of the most common candidates for use as therapeutic agents or efficient gene delivery systems. Efforts are being made to improve and perfect viral-vector-based therapies to overcome potential or reported drawbacks. Some preclinical trials of viral vector vaccines have yielded positive results, indicating their potential as prophylactic or therapeutic vaccine candidates. Utilization of the oncolytic activity of viruses is the future of cancer therapy, as patients will then be free from the harmful effects of chemo- or radiotherapy. This review discusses in vitro and in vivo studies showing the brilliant therapeutic potential of viruses.

Related collections

Most cited references 172

Record: found
Abstract: found
Article: found

Is Open Access

U1 snRNP regulates cancer cell migration and invasion in vitro

Jung-Min Oh, Christopher Venters, Chao Di … (2020)

Stimulated cells and cancer cells have widespread shortening of mRNA 3’-untranslated regions (3’UTRs) and switches to shorter mRNA isoforms due to usage of more proximal polyadenylation signals (PASs) in introns and last exons. U1 snRNP (U1), vertebrates’ most abundant non-coding (spliceosomal) small nuclear RNA, silences proximal PASs and its inhibition with antisense morpholino oligonucleotides (U1 AMO) triggers widespread premature transcription termination and mRNA shortening. Here we show that low U1 AMO doses increase cancer cells’ migration and invasion in vitro by up to 500%, whereas U1 over-expression has the opposite effect. In addition to 3’UTR length, numerous transcriptome changes that could contribute to this phenotype are observed, including alternative splicing, and mRNA expression levels of proto-oncogenes and tumor suppressors. These findings reveal an unexpected role for U1 homeostasis (available U1 relative to transcription) in oncogenic and activated cell states, and suggest U1 as a potential target for their modulation.

0 comments Cited 1523 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial

Feng-Cai Zhu, Yu-Hua Li, Xu-Hua Guan … (2020)

Summary Background A vaccine to protect against COVID-19 is urgently needed. We aimed to assess the safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 (Ad5) vectored COVID-19 vaccine expressing the spike glycoprotein of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain. Methods We did a dose-escalation, single-centre, open-label, non-randomised, phase 1 trial of an Ad5 vectored COVID-19 vaccine in Wuhan, China. Healthy adults aged between 18 and 60 years were sequentially enrolled and allocated to one of three dose groups (5 × 1010, 1 × 1011, and 1·5 × 1011 viral particles) to receive an intramuscular injection of vaccine. The primary outcome was adverse events in the 7 days post-vaccination. Safety was assessed over 28 days post-vaccination. Specific antibodies were measured with ELISA, and the neutralising antibody responses induced by vaccination were detected with SARS-CoV-2 virus neutralisation and pseudovirus neutralisation tests. T-cell responses were assessed by enzyme-linked immunospot and flow-cytometry assays. This study is registered with ClinicalTrials.gov, NCT04313127. Findings Between March 16 and March 27, 2020, we screened 195 individuals for eligibility. Of them, 108 participants (51% male, 49% female; mean age 36·3 years) were recruited and received the low dose (n=36), middle dose (n=36), or high dose (n=36) of the vaccine. All enrolled participants were included in the analysis. At least one adverse reaction within the first 7 days after the vaccination was reported in 30 (83%) participants in the low dose group, 30 (83%) participants in the middle dose group, and 27 (75%) participants in the high dose group. The most common injection site adverse reaction was pain, which was reported in 58 (54%) vaccine recipients, and the most commonly reported systematic adverse reactions were fever (50 [46%]), fatigue (47 [44%]), headache (42 [39%]), and muscle pain (18 [17%]. Most adverse reactions that were reported in all dose groups were mild or moderate in severity. No serious adverse event was noted within 28 days post-vaccination. ELISA antibodies and neutralising antibodies increased significantly at day 14, and peaked 28 days post-vaccination. Specific T-cell response peaked at day 14 post-vaccination. Interpretation The Ad5 vectored COVID-19 vaccine is tolerable and immunogenic at 28 days post-vaccination. Humoral responses against SARS-CoV-2 peaked at day 28 post-vaccination in healthy adults, and rapid specific T-cell responses were noted from day 14 post-vaccination. Our findings suggest that the Ad5 vectored COVID-19 vaccine warrants further investigation. Funding National Key R&D Program of China, National Science and Technology Major Project, and CanSino Biologics.

0 comments Cited 709 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Adeno-Associated Virus (AAV) as a Vector for Gene Therapy

Michael Naso, Brian E. Tomkowicz, William L. Perry … (2017)

There has been a resurgence in gene therapy efforts that is partly fueled by the identification and understanding of new gene delivery vectors. Adeno-associated virus (AAV) is a non-enveloped virus that can be engineered to deliver DNA to target cells, and has attracted a significant amount of attention in the field, especially in clinical-stage experimental therapeutic strategies. The ability to generate recombinant AAV particles lacking any viral genes and containing DNA sequences of interest for various therapeutic applications has thus far proven to be one of the safest strategies for gene therapies. This review will provide an overview of some important factors to consider in the use of AAV as a vector for gene therapy.

0 comments Cited 293 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Musab bin Umair: musab.umair@cemb.edu.pk

Fujimura Nao Akusa: fujimura.akusa@cemb.edu.pk

Hadia Kashif: hadia.kashif@cemb.edu.pk

Seerat-e-Fatima: seeratefatima@cemb.edu.pk

Fatima Butt: fatima.butt@cemb.edu.pk

Marium Azhar: marium.azhar@cemb.edu.pk

Iqra Munir: iqra.munir@cemb.edu.pk

Muhammad Ahmed: muhammad.ahmed@cemb.edu.pk

Wajeeha Khalil: wajeeha.khalil@cemb.edu.pk

Hafiz Sharyar: hafiz.sharyar@cemb.edu.pk

Shazia Rafique: shazia.rafique@cemb.edu.pk

Muhammad Shahid: shahidimran_gcu@yahoo.com

Samia Afzal:

ORCID: http://orcid.org/0000-0002-3298-5735

samiaraza@live.com

Journal

Journal ID (nlm-ta): Arch Virol

Journal ID (iso-abbrev): Arch Virol

Title: Archives of Virology

Publisher: Springer Vienna (Vienna )

ISSN (Print): 0304-8608

ISSN (Electronic): 1432-8798

Publication date (Electronic): 24 April 2022

Pages: 1-18

Affiliations

GRID grid.11173.35, ISNI 0000 0001 0670 519X, Centre of Excellence in Molecular Biology (CEMB), , University of the Punjab, ; 87-West Canal Bank Road, Thokar Niaz Baig, Lahore, Pakistan

Author notes

Handling Editor: Sheela Ramamoorthy.

Author information

Samia Afzal http://orcid.org/0000-0002-3298-5735

Article

Publisher ID: 5432

DOI: 10.1007/s00705-022-05432-8

PMC ID: 9035288

PubMed ID: 35462594

SO-VID: cdc02210-75ed-4cdc-a621-51d7e4eb635b

License:

This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

Viruses as tools in gene therapy, vaccine development, and cancer treatment

Read this article at

Abstract

Related collections

Wiley: Novel Coronavirus COVID-19

Most cited references 172

U1 snRNP regulates cancer cell migration and invasion in vitro

Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial

Adeno-Associated Virus (AAV) as a Vector for Gene Therapy

Author and article information

Contributors

Journal

Affiliations

Author notes

Author information

Article

History

Categories

Comments

Comment on this article

Similar content 328

Cited by 10

Most referenced authors 8,871