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germline cell gene therapy

'Some (transgenic) animals have been genetically engineered. The functioning allele they have received may also be passed on to the animals offspring. This is not the case with somatic cell gene therapy.'

But then how can introducing a gene into a cell cause that gene to be passed on? I don't understand how it can be passed on if it's not attached to any chromosome, or is it?
Reply 1
Because in germline the genes are introduced to the gametes.
Reply 2
Original post by AmyLH
Because in germline the genes are introduced to the gametes.


Thank you :smile: I have another question. Why don't the specialized cells containing the gene divide to pass on the allele for somatic cell therapy? I thought that whenever a cell replicated a genetically identical cell is made.:confused: So why doesn't it happen in this case?
Original post by AmyLH
Because in germline the genes are introduced to the gametes.


Horray for F215. :cool: Wow.. I got the same exams as you... except for the C3. and D1 in which case I am doing M1. :smile:
(edited 11 years ago)
Reply 4
Original post by tammie94
Thank you :smile: I have another question. Why don't the specialized cells containing the gene divide to pass on the allele for somatic cell therapy? I thought that whenever a cell replicated a genetically identical cell is made.:confused: So why doesn't it happen in this case?


Because in somatic the gametes aren't affected, just the body cells, so the change isn't passed on.
Reply 5
Original post by Future_Dr
Horray for F215. :cool: Wow.. I got the same exams as you... except for the C3. and D1 in which case I am doing M1. :smile:


I'm surprised with how much I remember to be honest! C3 is a resit :redface: be glad you don't have D1, it is so bloody boring :rolleyes:
Reply 6
Original post by AmyLH
Because in somatic the gametes aren't affected, just the body cells, so the change isn't passed on.


But it's passed on in bacteria so why not in humans?
Reply 7
Original post by tammie94
But it's passed on in bacteria so why not in humans?


That I cannot remember, sorry! :redface:
Reply 8
Original post by AmyLH
That I cannot remember, sorry! :redface:


okay :frown: I'll just keep researching.

Thanks anyway. :smile:
Original post by tammie94
But it's passed on in bacteria so why not in humans?


How do bacteria replicate? Do they require gametes?
Reply 10
Original post by indifferencepersonified
How do bacteria replicate? Do they require gametes?


OK but when a mutation occurs then why do cancerous cells form then? And cancerous cells are genetically identical to each other, right? So how does this happen?
Original post by tammie94
OK but when a mutation occurs then why do cancerous cells form then? And cancerous cells are genetically identical to each other, right? So how does this happen?


Cancer is a multi-step process and it is not true that all 'cancer cells' in a given tumour are the same, they have different mutations and chromosomal abnormalities. However, I think what you're getting at is how are genes/alleles inherited from one cell to the next.

So, in cancer a single cell may acquire a number of mutations in key genes which allow it to replicate uncontrollably (I'm not sure what level this is pitched at so if you want more info on this then ask). During mitosis, DNA is replicated (almost exactly) and the chromatids are separated into the 2 daughter cells, hence the 2 daughter cells have identical genomes which in turn are identical to the parent cell. The problem with cancerous cells is that replication is no longer under the bodies control, in addition the cancerous cells can gain a number of functions (invasion and metastasis being the 2 features that define the lesion as malignant), the end result being that you have cells in the tissues that can't be controlled which can result in a number of issues.
Reply 12
Original post by indifferencepersonified
Cancer is a multi-step process and it is not true that all 'cancer cells' in a given tumour are the same, they have different mutations and chromosomal abnormalities. However, I think what you're getting at is how are genes/alleles inherited from one cell to the next.

So, in cancer a single cell may acquire a number of mutations in key genes which allow it to replicate uncontrollably (I'm not sure what level this is pitched at so if you want more info on this then ask). During mitosis, DNA is replicated (almost exactly) and the chromatids are separated into the 2 daughter cells, hence the 2 daughter cells have identical genomes which in turn are identical to the parent cell. The problem with cancerous cells is that replication is no longer under the bodies control, in addition the cancerous cells can gain a number of functions (invasion and metastasis being the 2 features that define the lesion as malignant), the end result being that you have cells in the tissues that can't be controlled which can result in a number of issues.


Ok but shouldn't mitosis always result in genetically identical cells though?

Sorry for all the questions. I just don't understand this.
Original post by tammie94
Ok but shouldn't mitosis always result in genetically identical cells though?

Sorry for all the questions. I just don't understand this.


This is slightly off the idea of gene therapy now.

Mitosis involves the replication of the whole genome such that each daughter cell can receive a complete set of chromosomes each. Theoretically, mitosis will result in 2 identical daughter cells, but mitosis is not a perfect system and mistakes occur (most are resolved, some are not). These mistakes can then be incorporated into the daughter cells and so one might say the genome of that cell has been altered.
Reply 14
Original post by indifferencepersonified
This is slightly off the idea of gene therapy now.

Mitosis involves the replication of the whole genome such that each daughter cell can receive a complete set of chromosomes each. Theoretically, mitosis will result in 2 identical daughter cells, but mitosis is not a perfect system and mistakes occur (most are resolved, some are not). These mistakes can then be incorporated into the daughter cells and so one might say the genome of that cell has been altered.


Yeah that's what I'm confused about, in gene therapy genes have been added to the cell, so I'm confused about why this change to the cell isn't passed on to the daughter cells when it replicates.
Reply 15
Original post by tammie94
Yeah that's what I'm confused about, in gene therapy genes have been added to the cell, so I'm confused about why this change to the cell isn't passed on to the daughter cells when it replicates.


It will be passed on to the daughter cells of the cell in question, but not to the progeny of the organism.

This is pretty much what defines the germline and the soma. The germline refers to cells that are potentially inherited (i.e. the gametes). The soma refers to cells of the body that cannot give rise to gametes.
Original post by tammie94
Yeah that's what I'm confused about, in gene therapy genes have been added to the cell, so I'm confused about why this change to the cell isn't passed on to the daughter cells when it replicates.


If the gene has been successfully incorporated into the cell then it will be passed on to its daughter cells. As the above poster says, there is a distinction between somatic cells (of the body which make up the functional tissues, e.g. heart) and the germ cells (cells which can give rise to gametes and therefore be used procreate). If the gene is incorporated into a somatic cell, then it will be passed onto its daughter cells but not onto offspring, whereas if the gene is incorporated into a germ cell then it has the potential to be passed on to the parents offspring.
Reply 17
Original post by indifferencepersonified
This is slightly off the idea of gene therapy now.

Mitosis involves the replication of the whole genome such that each daughter cell can receive a complete set of chromosomes each. Theoretically, mitosis will result in 2 identical daughter cells, but mitosis is not a perfect system and mistakes occur (most are resolved, some are not). These mistakes can then be incorporated into the daughter cells and so one might say the genome of that cell has been altered.



Original post by Ashnard
It will be passed on to the daughter cells of the cell in question, but not to the progeny of the organism.

This is pretty much what defines the germline and the soma. The germline refers to cells that are potentially inherited (i.e. the gametes). The soma refers to cells of the body that cannot give rise to gametes.



Original post by indifferencepersonified
If the gene has been successfully incorporated into the cell then it will be passed on to its daughter cells. As the above poster says, there is a distinction between somatic cells (of the body which make up the functional tissues, e.g. heart) and the germ cells (cells which can give rise to gametes and therefore be used procreate). If the gene is incorporated into a somatic cell, then it will be passed onto its daughter cells but not onto offspring, whereas if the gene is incorporated into a germ cell then it has the potential to be passed on to the parents offspring.


But it says in the book that 'Introduction into somatic cells means that any treatment is short lived and has to be repeated regularly. The specialized cells containing the gene will not divide to pass on the allele'. It actually makes sense for the gene not to be passed onto the daughter cells, because if you think about it in mitosis the spindle fibres attach to chromosomes so it cannot attach onto an individual gene as the genes being there in the first place isn't natural. Do you guys agree? Or am I wrong?
Reply 18
Original post by tammie94
But it says in the book that 'Introduction into somatic cells means that any treatment is short lived and has to be repeated regularly. The specialized cells containing the gene will not divide to pass on the allele'. It actually makes sense for the gene not to be passed onto the daughter cells, because if you think about it in mitosis the spindle fibres attach to chromosomes so it cannot attach onto an individual gene as the genes being there in the first place isn't natural. Do you guys agree? Or am I wrong?


Somatic cell therapy encompasses many different treatments, so it is difficult to say exactly why. Viral vectors are often used to transduce cells, and most of these will stably integrate into the chromosome. Vectors that stably integrate into the chromosome will be passed onto daughter cells by mitosis (if the recipient does actually divide).

The use of viral vectors that integrate into the chromosomes has been reduced because they are highly carcinogenic. Consequently, researchers have resorted to the use of vectors that do not stably integrate into the chromosome. While these have little chance of inducing cancer, they will not be stably inherited in progeny cells due to lack of chromosomal integration. This is one reason why somatic cell therapy can have only transient benefits.

From that quote in your book, it seems like they are referring to the addition of a gene to non-dividing cells (i.e. differentiated cell). This means that the transgene will be lost whenever the recipient cells in question die. This is another reason why somatic cell therapy may be short-lived. The only way to get round this really is to transduce stem cell ex vivo and then reintroduce them into the patient. As they are stem cells, they will divide repeatedly to reconstitute the transgenic stem cell pool.

So in summary, there are two reasons why the somatic cell therapy may be short-lived:
1) In dividing cells in which the vector is not stably inherited in the daughter cells due to lack of chromosomal integration
2)In non-dividing recipient cells, in which the transgene will be eliminated whenever the recipient cell dies.

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