Gene therapy

[novawildcat]

I was possibly interested in pursuing drug delivery systems during graduate school for a biomedical engineering program this coming summer. Some questions I have about gene therapy since my background does not include heavy training in biology:

1.) How can we ever use gene therapy to treat disease that are related to more than 1 gene malfunctioning? I mean some of the biggest disease states out there like arthritis, heart disease, and parkinson's are believe to be multi gene related correct? I could see gene therapy working for a disease like sickle cell anemia, where only 1 gene needs to be replaced, but how in the world could you specifically target more than 1 chromosome?

2.) A lot of research over the past 20 years has been focused simply on trying to deliver a gene to specific cells within a certain type of tissue. However, this doesn't address anything at all about what happens at the subcellular level. Say someone comes up with an awesome new delivery system to deliver genes to a desired specific cell, there's still the problem of making sure that the gene you delivered gets incorporated into chromosomes at the precise location correct? If you introduce a gene into the nucleus and it gets inserted into the wrong chromosome at the wrong position you could cause a whole slew of other problems like frame shift mutations correct? Is there any research being done right now that addresses the issue of gene therapy delivery at the subcellular level? I have yet to come across any. Or does it not matter once a gene is delivered into the nucleus? Does the cell contain any machinery that can incorporate a exogenously supplied gene into its proper place in the genome?


Now combine 1 and 2 together and you can see that I'm quite skeptical that gene therapy will ever work for many diseases out there. If you are trying to treat a disease that is multi gene related AND you must also be able to control for multiple genes to make sure that they get delivered and incorporated into chromosomes in the exact spots then the problems with gene therapy seem to rise exponentially. Is there any hope for this field?


These are just some random thoughts I had before potentially pursuing a 6 year research project on the subject during grad school. Thanks.

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[gbwillner]

I was possibly interested in pursuing drug delivery systems during graduate school for a biomedical engineering program this coming summer. Some questions I have about gene therapy since my background does not include heavy training in biology:

1.) How can we ever use gene therapy to treat disease that are related to more than 1 gene malfunctioning? I mean some of the biggest disease states out there like arthritis, heart disease, and parkinson's are believe to be multi gene related correct? I could see gene therapy working for a disease like sickle cell anemia, where only 1 gene needs to be replaced, but how in the world could you specifically target more than 1 chromosome?

2.) A lot of research over the past 20 years has been focused simply on trying to deliver a gene to specific cells within a certain type of tissue. However, this doesn't address anything at all about what happens at the subcellular level. Say someone comes up with an awesome new delivery system to deliver genes to a desired specific cell, there's still the problem of making sure that the gene you delivered gets incorporated into chromosomes at the precise location correct? If you introduce a gene into the nucleus and it gets inserted into the wrong chromosome at the wrong position you could cause a whole slew of other problems like frame shift mutations correct? Is there any research being done right now that addresses the issue of gene therapy delivery at the subcellular level? I have yet to come across any. Or does it not matter once a gene is delivered into the nucleus? Does the cell contain any machinery that can incorporate a exogenously supplied gene into its proper place in the genome?


Now combine 1 and 2 together and you can see that I'm quite skeptical that gene therapy will ever work for many diseases out there. If you are trying to treat a disease that is multi gene related AND you must also be able to control for multiple genes to make sure that they get delivered and incorporated into chromosomes in the exact spots then the problems with gene therapy seem to rise exponentially. Is there any hope for this field?


These are just some random thoughts I had before potentially pursuing a 6 year research project on the subject during grad school. Thanks.

1) probably not useful for anything other than gene haploinsufficiency diseases. That pretty much eliminates all the stuff you mention, but it would be good for things like cystic fibrosis and hemophilia.

2). While specific expression levels may be necessary for thinkgs like transcription factors, many mendelian disorders are caused by a complete lack of expression of a protein. In such cases, the gene would not have to be in the correct chromosomal location (or even in a chromosome) to function. That said, the major problem with gene therapy (aside from targeting and transfection problems) is immune incompatibility. Basically, and new protein made by your body as a result of gene therapy may be recognized as "foreign" by your immune system and be distroyed. It may even cause major autoimmunie problems for the patient. This is basicalyl why you haven't heard too many people talk about gene therapy in a decade.

Gene therapy was/is not intended to cure all disease- that would be foolish, since not all disease is genetic.