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Mohamed A1-Rubeai
possible that although the product of bcl-2 gene can repress apoptosis in
conditions of excess oxygen, the high level of necrosis resulting from the severe
injury to cellular structures can lead to an apparent reduction of cell growth
promotion.
The benefit for cell culture from the overexpression of anti-apoptotic genes
can, therefore, only be realised in normal conditions or conditions of mild stress
which do not lead to high level of necrosis or cell destruction. Such conditions
are normally encountered in high cell density cultures where cells are continuously under nutrient limitation leading to reduction in growth rate and also cell
death with consequent problems arising from cell lysis and the release of DNA,
proteases, etc.
The large scale production of vaccines in animal cells requries a relatively
sophisticated processes utilising a suitable cell-virus system and appropriate
production technology. With the tremendous demand on producing viruses as
rapidly, cheaply and efficiently, as possible there is a need for extending the cell
life cycle to allow more viral replication cycles. It has been reported that
apoptosis occurs on infection of the cells by many viruses including the chicken
anemia virus [102], human immunodeficiency virus type 1 [103], influenza
A and B viruses [104] and insect baculovirus [105]. The hypothesis was
presented that interference by the virus in the intracellular and intercellular
signalling could cause abnormal induction of an activation-associated cellsuicide process by apoptosis. On the other hand, a number of other viruses have
been found to possess genes, such as p35, which can prevent apoptotic cell death
in their host cells [105, 106].
Recognising the importance of apoptosis in virus infection may have dramatic consequences for the conception of new strategies of research and development for enhancement of viral yield (and of expressed product in the case of
recombinant virus) in vaccine production and gene therapy processes. In order
to prevent apoptosis, antiapoptotic genes should be overexpressed in either the
viruses or the infected cells, thereby allowing the cells to survive longer and the
viruses to multiply further.
In closing, I would like to point out that the first half of the 1990s has
resulted in an explosion of knowledge and information about the characteristics
and occurrence of apoptosis as well as the physiological and non-physiological
triggers, molecular pathways and genes involved in the death and survival
process. The second half of the 1990s will, undoubtedly, witness a giant leap
towards the realisation of our goals to develop drugs that inhibit apoptosis
induced by infection and drugs that stimulate apoptosis for the treatment of
cancers. In addition to the obvious relevance of this knowledge to human
therapies, they may also be of importance for the industrial production of
biologics. In this respect, the development by genetic manipulation of robust cell
lines superior in their growth and productivity as well as the optimisation of the
physiological environment for the large scale cultivation of cell lines should lead
to efficient and safe processing of protein products and reduction of contaminated products such as DNA and proteases.
Mohamed A1-Rubeai
possible that although the product of bcl-2 gene can repress apoptosis in
conditions of excess oxygen, the high level of necrosis resulting from the severe
injury to cellular structures can lead to an apparent reduction of cell growth
promotion.
The benefit for cell culture from the overexpression of anti-apoptotic genes
can, therefore, only be realised in normal conditions or conditions of mild stress
which do not lead to high level of necrosis or cell destruction. Such conditions
are normally encountered in high cell density cultures where cells are continuously under nutrient limitation leading to reduction in growth rate and also cell
death with consequent problems arising from cell lysis and the release of DNA,
proteases, etc.
The large scale production of vaccines in animal cells requries a relatively
sophisticated processes utilising a suitable cell-virus system and appropriate
production technology. With the tremendous demand on producing viruses as
rapidly, cheaply and efficiently, as possible there is a need for extending the cell
life cycle to allow more viral replication cycles. It has been reported that
apoptosis occurs on infection of the cells by many viruses including the chicken
anemia virus [102], human immunodeficiency virus type 1 [103], influenza
A and B viruses [104] and insect baculovirus [105]. The hypothesis was
presented that interference by the virus in the intracellular and intercellular
signalling could cause abnormal induction of an activation-associated cellsuicide process by apoptosis. On the other hand, a number of other viruses have
been found to possess genes, such as p35, which can prevent apoptotic cell death
in their host cells [105, 106].
Recognising the importance of apoptosis in virus infection may have dramatic consequences for the conception of new strategies of research and development for enhancement of viral yield (and of expressed product in the case of
recombinant virus) in vaccine production and gene therapy processes. In order
to prevent apoptosis, antiapoptotic genes should be overexpressed in either the
viruses or the infected cells, thereby allowing the cells to survive longer and the
viruses to multiply further.
In closing, I would like to point out that the first half of the 1990s has
resulted in an explosion of knowledge and information about the characteristics
and occurrence of apoptosis as well as the physiological and non-physiological
triggers, molecular pathways and genes involved in the death and survival
process. The second half of the 1990s will, undoubtedly, witness a giant leap
towards the realisation of our goals to develop drugs that inhibit apoptosis
induced by infection and drugs that stimulate apoptosis for the treatment of
cancers. In addition to the obvious relevance of this knowledge to human
therapies, they may also be of importance for the industrial production of
biologics. In this respect, the development by genetic manipulation of robust cell
lines superior in their growth and productivity as well as the optimisation of the
physiological environment for the large scale cultivation of cell lines should lead
to efficient and safe processing of protein products and reduction of contaminated products such as DNA and proteases.