Expert: Florence M Rollwagen - 10/11/2008

Question
hi florence.. i wanted to know how gene therapy can be used to prevent inhertied diseases? im having trouble understanding why.. thankss

Answer
Hi Umayr:  Thanks for your question.  This is a very complex problem.  First, it would depend on the inherited disease we're talking about.  Second, it would depend on whether we knew what gene(s) were involved, and third, it would depend on getting the gene into the right cells at the right time.

So, here's a summary:

Let's say we know exactly what gene and exactly what it does, say sickle cell disease.  We know that it's a simple single nucleotide substitution of thymidine for adenine in one of the hemoglobin genes. (http://en.wikipedia.org/wiki/Sickle-cell_disease)

Then, we would have to engineer the correct DNA sequence for the correct hemoglobin molecule and put it into a viral vector.  The viral vector will enter the cell and insert DNA into the host genome.  But viral vectors are limited as to what size DNA they can insert, so here's another problem.  

Then, we have to worry whether the inserted normal hemoglobin gene gets into the correct cell and the correct sequence.  Is it inserted backwards?  Has it been degraded before insertion?  Does it have the correct reading frame and starter sequences? (to mention a few problems!)

Then we have to make sure that it's in the right cells (blood cell precursors in the marrow).

Then we have to make sure it's a stable insert, and will not be expelled by the cell.

Then we have to make sure the virus doesn't cause cancer in the host (that's been happening too).

Take a look at this site:  http://en.wikipedia.org/wiki/Gene_therapy and see if you understand any better.

Write back if you have more questions.

FM Rollwagen, PhD