I am interested in learning about attempts to treat adult individuals suffering from a genetic disease in which the underlying changes in the DNA of the gene are understood.

(i) Are there approaches that use drugs or do they use DNA corresponding to the normal DNA?

(ii) Are there attempts to reverse the condition or only ammeliorate it?

(iii) How near is such gene therapy to clinical use and for which diseases?

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    $\begingroup$ What you're interested in is a form of Gene Therapy. This is extremely difficult. There are many strategies currently being researched, and the best strategy to use probably depends on the specific genetic condition. In your question, you mention gene editing, which uses CRISPR/Cas9, Zinc Finger Nucleases, or TALEN endonucleases to cut DNA at a specific site, then relies on the cell's DNA repair mechanism to fix the cut, hopefully with a correct of the gene provided alongside the nuclease enzyme. This is very inefficient in cell culture, but at least in cell culture you can find a good cell $\endgroup$
    – user137
    Commented May 29, 2016 at 11:11
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    $\begingroup$ and grow as many copies as you need. In a living organism, it becomes much harder. Most of the gene editing nucleases are delivered as a molecule of DNA or mRNA that can then make the enzyme once it gets into a cell. However, delivery of DNA to cells in vivo is an incredible challenge. Modified viruses are more effective than nonviral systems, but have limited carrying capacity and possible immunological effects. Nonviral systems are in still in their infancy after over 20 years of effort. A nonviral gene delivery system must protect DNA from destruction by nucleases, get the DNA into the $\endgroup$
    – user137
    Commented May 29, 2016 at 11:15
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    $\begingroup$ right cell type, and then get that DNA into the nucleus. Once in the nucleus, the DNA can make the protein, in our case a gene editing nuclease. Now the nuclease must find and cut the bad gene in the right way, if using CRISPR, that requires a small guide RNA to target the enzyme to the right place. Depending on how this RNA is delivered, not all cells that get a copy of the CRISPR gene will get the RNA, so these cells will not have their DNA cut. Using ZFN or TALENS avoids the guide RNA requirement, but often have a worse accuracy rate and can cut the DNA at incorrect positions. $\endgroup$
    – user137
    Commented May 29, 2016 at 11:18
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    $\begingroup$ But the biggest barrier to efficient gene editing is probably homology directed repair. When DNA is cut, your cells have 2 ways to fix it, they can just stick the ends together and fill in the gaps. This usually introduces errors and can often simply destroy a gene, and is usually not desired in gene editing, but it's much more efficient. Homology Directed Repair will take a matching copy of the damaged DNA, usually the corresponding gene on the sister chromatid, and use it to copy the sequence into the damaged DNA. This is what allows gene editing to work, but you have to deliver your good $\endgroup$
    – user137
    Commented May 29, 2016 at 11:21
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    $\begingroup$ @user137 You couldv'e just put this as an answer, I believe you're right! $\endgroup$ Commented May 29, 2016 at 12:55

1 Answer 1


The scope of this question is too wide to be answered on Biology SE. However I will give you very brief answers to your questions (as I have rephrased them) and point you towards some sources of basic information on the Internet. After reading these you may wish to return with more specific questions. I have also briefly summarized some of the problems which it is useful to be aware of before reading details of specific approaches to gene therapy,.


(i) Some approaches involve attempts to replace a defective gene with a functional gene or add the latter to the patient’s DNA. Others involve drugs, often nucleic acid in nature.

(ii) Current efforts often have the more modest aim of ameliorating the disease, although there are also efforts to reverse the condition.

(iii) Gene therapy is not yet in general clinical use, although for some diseases (e.g. Severe Combined Immune Deficiency and Chronic Granulomatus Disorder) there have been reports of success in limited clinical trials.

General Reading

I am not an expert in this area, but by Googling for ‘Gene Therapy’ I came up with the following pages that you may find helpful.

Your Genome

University of Utah: Approaches to Gene Therapy

American Society of Cell and Gene Therapy

You may also be interested to read about the currently controversial drug, Eteplirsen.

Problems in Gene Therapy

Rather than giving you details of technical approaches to gene therapy, for which you may not have the necessary scientific background, I draw your attention to some of the key problems and questions that have to be addressed in this area.

  1. Does one need to counteract the harmful effect of a mutant gene product (e.g. sickle cell haemoglobin), or is it sufficient to produce a ‘good’ gene product to remedy a deficit?
  2. Is it possible to target new cells or does one have to deal with existing mature cells? (Some cells like blood and immune cells are constantly renewing themselves, whereas others like muscle turn over much more slowly. The latter are more difficult to deal with.)
  3. How can the DNA (or drug) be deliverdd to the cell, and only to the appropriate cell. (A variety of delivery techniques have been employed in different circumstances.)
  4. How can the therapeutic DNA be incorporated into the appropriate position in the genome, and how can one ensure that it is expressed, and that no other genes are affected. (Early attempts at gene therapy using in which DNA was inserted at the wrong position resulted in cancers. However technology here is moving rapidly.)
  • $\begingroup$ "Early attempts at gene therapy using in which DNA was inserted at the wrong position resulted in cancers." - what are some examples of this? $\endgroup$
    – meow
    Commented Jul 14, 2016 at 20:28
  • $\begingroup$ @mingyeow The most well-known is the attempt to cure SCID in 2002. See Gene Therapy (2003) 10, 4–4. doi:10.1038/sj.gt.3301946. $\endgroup$
    – David
    Commented Jul 14, 2016 at 20:57
  • $\begingroup$ thank you! this indirectly answers one of my main questions in gene therapy: how is it possible to control the side effects of gene mutation? what would be your recommended reading for understanding how we are controlling how cells whose genes have been changed are inserted into the target organism's body? $\endgroup$
    – meow
    Commented Jul 14, 2016 at 21:36
  • $\begingroup$ @mingyeow This isn't really my field, but from general reading I am aware that there is a lot of interest in using CRISPR technology because of its precision. A recent commentary I found surfing might be a good starting point: $\endgroup$
    – David
    Commented Jul 14, 2016 at 22:25
  • $\begingroup$ I understand that crispr offers precision in gene editing, but does that also apply to the way cells reproduce those edited genes? $\endgroup$
    – meow
    Commented Jul 15, 2016 at 0:36