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Gene therapy

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Gene therapy

Postby Frank » Wed Mar 09, 2005 11:44 am

My girlfriend is thinking about joining a lab that works on gene therapy with lentiviral vectors for her PhD research. Since gene therapy is in the news regularly, in both positive and negative ways, I would like to ask whether people consider it a wise choice as a topic for PhD research. She herself is very excited about gene therapy from attending talks at a conference, and she also likes the adviser, who has a good reputation in the field, and the people in the lab. After her PhD, she would like to work in the biotech or pharmaceutical industry. What are the possibilities there?
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Gene therapy

Postby Dave Jensen » Wed Mar 09, 2005 12:30 pm

While every niche has its own ups and downs, and I can only speak for industry needs, I must warn you that at this particular time, those who have a strong background in gene therapy are finding it is hard to get a job. There is mixed interest on this area of research in industry; companies who are NOT in the gene therapy field see these CV's as those who are "in a very fine niche" and they don't see the broad applications of what that person has learned. Instead, employers tend to focus in on the fact that these employees are "unique" and don't fit in well with their companies. In short, it may be a difficult area from which to pursue industry jobs.

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Gene therapy

Postby Adam » Wed Mar 09, 2005 1:57 pm

Frank,
I have mixed feeling about lentiviral vectors. Lentiviruses such as HIV tend to insert into genes and even exons. There were reports on occurrence of rare lymphoproliferation in patients after gene therapy treatments with lentivirus-transduced CD34+cells. This raised very serious questions about safety of current retrovirus vectors. I think FDA stopped all similar experiments some years ago.

This topic is very exciting for retrovirologists, the explanations of the insertion preference will take some time but definitely will hit major journals - Cell/Nature/Science. On the other hand, industrial applications (given the FDA position) are questionable. Very likely, a long experience with gene delivery may help, she will face many general problems such as transgene silencing by methylation. But unless we will find some retrovirus with _very_ different insertion preferences (unlikely), other vectors may be more perspective. If she can concentrate on some general problems of gene therapy (transgene silencing), it would be probably much better. Otherwise unless she will work in a very top-level lab (such as F. Bushman @upenn), I don?t think this is the best way to enter the industry.

My advices:
1. she should read these papers - Schroder et al. 2002 Cell 110: 521-529; Wu et al. 2003 Science 300:1749-1751; Mitchell et al. 2004 PLoS Biol. 2(8):E234.

This commentary in Gene Therapy is obligatory: ?Risks and benefits of gene therapy for immunodeficiency: a reality check? Gene Therapy (2002) 9, 1561?1562. (http://www.nature.com/gt/Editorial.pdf)

2. With this knowledge, she should ask her prospective boss about his/her opinion on these issues. If the PI tries to describe the problems as minor, he/she is not playing fair game and would recommend refusing the position. If, on the other hand, the future PI is serious about it, she may try to design a research project oriented on general problems of gene therapy that are independent of the vectors used ? for example transgene silencing, methylation, etc.

This is my perspective from an academic point of view. I don?t have any idea what is the general situation of gene therapy in industry. Someone else should answer it.

A.
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Gene therapy

Postby Lora » Wed Mar 09, 2005 2:10 pm

From what I've read about the state of gene therapy, it'll be decades before any gets implemented in an application. Mostly killed by catastrophic failures (Jesse Gelsinger et al.), it's getting thumbs-down more recently due to the coming implementation of array diagnostics: we're finding out that a great many things we thought we knew about genetics are crap.

As far as lentiviral vectors go, they're still useful as model systems and tools. If she really likes doing lentivirus transfections and is determined to go into applications (i.e. industry), she might consider immunology. She can do transfections for immunodeficient models to her heart's content, and there's enough cell/molec and physiology involved that it's feasible to branch out into other fields if she decides she doesn't like it.
Lora
 

Gene therapy

Postby Andy » Wed Mar 09, 2005 4:05 pm

People with experience in gene therapy using lentiviral vectors may find some interest in industry on the target validation side. Several companies are using viral-based RNAi techniques to evaluate potential drug targets by knocking them out via virus in model systems.

As a therapy I'm skeptical, and I used to work at a "gene therapy" company. But as a tool for research, the techniques are usefull and marketable in some companies.

Andy
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Gene therapy

Postby Kevin Foley » Wed Mar 09, 2005 6:49 pm

Most people do academic postdocs before jumping to industry. Assuming she doesn't do a postdoc in the same field, her focus on gene therapy as a grad student shouldn't hurt her and may even help her eventually find a job in industry.

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Gene therapy

Postby Kate » Thu Mar 10, 2005 1:07 am

I am currently doing a post-doc in the gene therapy field working with adeno-associated virus (AAV), which is generally considered one of the safer viral vectors. I received my PhD in Pharmacology, so my perspective tends to be much different than those I work for, who come from a virology background. Generally speaking, I have found the people in the gene therapy field to be out of touch with reality in terms of the efficacy and safety of the therapy. It is not safe, and in many cases it is not necessary. At the moment, it is difficult to find funding outside of those who want to fund "daring and innovative" studies, or for the treatment of difficult and terminal conditions. I also have the feeling that gene therapy is less in vogue than previously, with some of the "mainstay" genetic conditions now focusing on drug interventions rather than gene therapy.

I have had success is the application of viral vectors to basic research. They are great for studying the role of proteins in biological processes (think of it as transient transgenics or knockouts is using RNAi). I have had two grants funded based upon this principle.

A post-doc left the lab in September to try he luck in industry. Even though there are many options in the Boston area, she has not had any real offers. There quite a few gene therapy companies, and companies centered around vector production and purification systems. However, I doubt there are enough jobs for all the qualified post-docs being churned out in this area.

Just my two cents...

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