Propagation of Adenoviral Vectors

Animal Cell Lines as Expression Platforms in Viral Vaccine Production: A Post Covid-19 Perspective

“…108,190 In addition, since detailed records are kept from the development stage, full characterization is made, and the cell banking system is shown in detail, this cell line meets all the requirement determined by the regulatory institutions. 108,188 In other studies, the oncogenicity and tumorigenicity of this cell line were evaluated using live cell injection, cellular DNA, cell lysate, and viral vector. While it has been shown that only high concentrations of live cell injection can induce tumor formation, it has been demonstrated that cell lysate, DNA and product did not trigger tumor formation at the injection site.…”

“…The aim of vaccine production is not only to protect public health and prevent diseases, but it also has a commercial concern, especially for private companies, and the companies that produce it also aim to make a profit. ,, For this reason, in order to achieve high efficiency in the shortest time, the expression platform to be used for vaccine production is required to have features such as high accuracy expression capacity, ability to be successfully propagated in serum-free media, short doubling time, high maximum cell concentration, and ability to reach high viral titers. ,,,,, At the same time, since some cell lines are patented within the scope of intellectual property rights, their use in commercial production creates additional costs, and this should be taken into consideration when choosing a cell line . In addition, the origins of some cellular substrates, especially those of human origin, may pose ethical, psychological, and religious problems. , …”

“…This cell line was created as a result of immortalization with the E1 gene region of adenovirus type 5, similar to HEK-293. , However, the PER.C6 cell line was immortalized in a way that it does not contain the full-length E1 gene region, as in the HEK-293 cell line. The reason for this, minimize the formation of undesirable replication-competent viral vectors as a result of homologous recombination that may occur due to the overlapping sequences of the HEK-293 cellular genome, which contains the entire E1 gene region, with the adenoviral vector structure used during the production of the replication-defective viral vector. , For this reason, PER.C6 was created with a DNA construct containing only nucleotides 459–3510 of the gene region encoding E1A and EB1 and containing human phosphoglycerate kinase as the promoter. ,, The purpose of this is to develop the PER.C6 cell line directly for use in replication-deficient viral vector vaccines and gene therapy products for the biotechnology industry to ensure high production safety. , In addition, since detailed records are kept from the development stage, full characterization is made, and the cell banking system is shown in detail, this cell line meets all the requirement determined by the regulatory institutions. , In other studies, the oncogenicity and tumorigenicity of this cell line were evaluated using live cell injection, cellular DNA, cell lysate, and viral vector. While it has been shown that only high concentrations of live cell injection can induce tumor formation, it has been demonstrated that cell lysate, DNA and product did not trigger tumor formation at the injection site.…”

“…The reason for this, minimize the formation of undesirable replication-competent viral vectors as a result of homologous recombination that may occur due to the overlapping sequences of the HEK-293 cellular genome, which contains the entire E1 gene region, with the adenoviral vector structure used during the production of the replication-defective viral vector. 108 , 190 For this reason, PER.C6 was created with a DNA construct containing only nucleotides 459–3510 of the gene region encoding E1A and EB1 and containing human phosphoglycerate kinase as the promoter. 108 , 189 , 190 The purpose of this is to develop the PER.C6 cell line directly for use in replication-deficient viral vector vaccines and gene therapy products for the biotechnology industry to ensure high production safety.…”

“… 108 , 190 For this reason, PER.C6 was created with a DNA construct containing only nucleotides 459–3510 of the gene region encoding E1A and EB1 and containing human phosphoglycerate kinase as the promoter. 108 , 189 , 190 The purpose of this is to develop the PER.C6 cell line directly for use in replication-deficient viral vector vaccines and gene therapy products for the biotechnology industry to ensure high production safety. 108 , 190 In addition, since detailed records are kept from the development stage, full characterization is made, and the cell banking system is shown in detail, this cell line meets all the requirement determined by the regulatory institutions.…”