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Cancer gene therapy goes viral: viral vector platforms come of age

Urban Bezeljak

Urban Bezeljak

COBIKAjdovščina, Slovenia
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Bezeljak, Urban
  
11. Feb. 2022
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Artikel-Kategorie: Review
Online veröffentlicht: 11. Feb. 2022
Seitenbereich: 1 - 13
Eingereicht: 25. Nov. 2021
Akzeptiert: 04. Jan. 2022
DOI: https://doi.org/10.2478/raon-2022-0002
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© 2022 Urban Bezeljak, published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Figure 1

Use of viral vectors in clinical trials to treat cancer. Overall, retrovirus viral family vectors are the most widespread. These include lenti- and gammaretroviruses, which are used in adoptive cell therapy. Other popular vectors for cancer treatment are adenovirus, poxvirus like vaccinia, herpes simplex virus (HSV) and adeno-associated virus (AAV). Measles virus, vesicular stomatitis virus (VSV) and poliovirus are some of the other vectors that are not explicitly depicted. Data on all open cancer trials are from Wiley Journal of Gene Medicine Gene Therapy Clinical Trials Worldwide database (retrieved October 2021).11
Use of viral vectors in clinical trials to treat cancer. Overall, retrovirus viral family vectors are the most widespread. These include lenti- and gammaretroviruses, which are used in adoptive cell therapy. Other popular vectors for cancer treatment are adenovirus, poxvirus like vaccinia, herpes simplex virus (HSV) and adeno-associated virus (AAV). Measles virus, vesicular stomatitis virus (VSV) and poliovirus are some of the other vectors that are not explicitly depicted. Data on all open cancer trials are from Wiley Journal of Gene Medicine Gene Therapy Clinical Trials Worldwide database (retrieved October 2021).11

Figure 2

Overview of adenovirus vector design. (A) Schematic representation of adenovirus structure. Adenoviruses are non-enveloped 90 nm particles with pointing fibre rods. (B) Outline of wild type adenovirus genome, the first-generation adenovirus vector plasmid and helper-dependent adenoviral vector plasmid with the transgene expression cassette. The wild type genome highlights key early genes, while other genetic elements are omitted for clarity. The first-generation adenovirus vector particles are assembled in HEK 293 cell line by transgene vector plasmid transfection. Additionally, the helper-dependent vector assembly also requires infection with a helper virus.ITR = inverted terminal repeat; dsDNA = double-stranded DNA; pDNA = plasmid DNA.
Overview of adenovirus vector design. (A) Schematic representation of adenovirus structure. Adenoviruses are non-enveloped 90 nm particles with pointing fibre rods. (B) Outline of wild type adenovirus genome, the first-generation adenovirus vector plasmid and helper-dependent adenoviral vector plasmid with the transgene expression cassette. The wild type genome highlights key early genes, while other genetic elements are omitted for clarity. The first-generation adenovirus vector particles are assembled in HEK 293 cell line by transgene vector plasmid transfection. Additionally, the helper-dependent vector assembly also requires infection with a helper virus.ITR = inverted terminal repeat; dsDNA = double-stranded DNA; pDNA = plasmid DNA.

Figure 3

Overview of AAV vector design. (A) Schematic representation of AAV structure. AAV virions are non-enveloped 25 nm icosahedral particles. (B) Outline of wild type AAV genome and AAV vector plasmid with the transgene expression cassette. AAV vector particles are assembled in adenoviral E1-expressing HEK 293 cell line, which is co-transfected with transgene AAV vector plasmid, a helper plasmid and a rep/cap plasmid. Alternatively, AAV vectors can be produced in insect cells, which are co-infected with ITR-flanked transgene and rep/cap recombinant baculoviruses.ITR = inverted terminal repeat; pDNA = plasmid DNA; ssDNA = single-stranded DNA
Overview of AAV vector design. (A) Schematic representation of AAV structure. AAV virions are non-enveloped 25 nm icosahedral particles. (B) Outline of wild type AAV genome and AAV vector plasmid with the transgene expression cassette. AAV vector particles are assembled in adenoviral E1-expressing HEK 293 cell line, which is co-transfected with transgene AAV vector plasmid, a helper plasmid and a rep/cap plasmid. Alternatively, AAV vectors can be produced in insect cells, which are co-infected with ITR-flanked transgene and rep/cap recombinant baculoviruses.ITR = inverted terminal repeat; pDNA = plasmid DNA; ssDNA = single-stranded DNA

Figure 4

Overview of lentivirus vector design. (A) Schematic representation of lentivirus structure. Lentiviruses are 100 nm enveloped particles with exposed glycoprotein that defines the virus and vector tropism.55 (B) Outline of wild type lentivirus genome and lentivirus vector plasmid with the transgene expression cassette. Only key genetic elements are highlighted in the genome structure, rest are omitted for clarity. Lentivirus particles are assembled in mammalian cell culture by co-transfection of four plasmids: the transgene plasmid, gag/pol and rev packaging plasmids and VSV-G expression plasmid.pDNA = plasmid DNA; ssRNA = single-stranded RNA; LTR= long terminal repeat
Overview of lentivirus vector design. (A) Schematic representation of lentivirus structure. Lentiviruses are 100 nm enveloped particles with exposed glycoprotein that defines the virus and vector tropism.55 (B) Outline of wild type lentivirus genome and lentivirus vector plasmid with the transgene expression cassette. Only key genetic elements are highlighted in the genome structure, rest are omitted for clarity. Lentivirus particles are assembled in mammalian cell culture by co-transfection of four plasmids: the transgene plasmid, gag/pol and rev packaging plasmids and VSV-G expression plasmid.pDNA = plasmid DNA; ssRNA = single-stranded RNA; LTR= long terminal repeat
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