We’re trying to change our lives by changing our eating style, by changing our lifestyles, going to the gym, smiling more. Does it help, all those efforts? Will it change our bodies, our genes, genomes of our children?
Figure 1. Epigenetic mechanisms involved in regulation of gene expression. Cytosine residues within DNA can be methylated, and lysine and arginine residues of histone proteins can be modified.
Me = methylation, Ac = acetylation, P = phosphorylation, Ub = ubiquitination.
Changes ‘on top’ of DNA need lots of time to get to stable phase but if it does it can be inherited by your children. Let’s say you like coffee. Did you parents like coffee too? Or you grandparents? There is a high probability that your children will also be coffee lovers. That’s called epigenetic.
Gene editing technology is an evolving area of clinical and translational research. Recently there have been many reports from the field of genetic engineering regarding the modification of genetic material of both plant and animal cells. A new light in this field has been thrown by the use of CRISPR technology, called by “molecular scissors” thanks to precise cutting DNA and the possibility of introducing modifications into specific DNA sequences. The molecular mechanism of this system has a chance to revolutionize gene therapy.
CRISPR is a natural bacteria immune system which allows bacteria that has previously survived viral infection to fight against other attacks and shred the invader DNA.
CRISPR is a kind of gift to scientists which allows to proceed research very quickly and provide practical way to solve problems like Sickle Cell Anemia disease, where we have understood the genetic cause for a long time but there was no possibility to treat patients, now it is possible to remove stem cells that produce blood cells and edit those cells and implement correction to the genetic code, the mutation that is responsible for the disease and replace those cells. That action would give patient new set of cells without mutation and which will produce healthy blood cells. It is possible that in five years we will be witnesses of clinical trials in that area.
There is also an idea of editing pigs DNA what will result in more human-like DNA and pigs therefore will be better organ donors for human. It could be also possible to remove viruses in pigs that would infect a patient.
Mosquitos are also a field of interest of gene editing using the technique called gene drive. Insects can spread viruses like Zika virus or Dengue virus and changing their DNA will cause mosquitos which would be unable to transmit viruses.
CRISPR will be able to alternate human evolution and anheance the abilities of people (which can be seen as eugenic practices) due to heritable changes it cause. It has implications in society as all and research using this technique are restricted. As of now stem cells editing is allowed, Directive 2001/20/EC does not allow germ line editing and eugenic practices.
Somatic Cell Therapies
Cells are removed from the patients engineered and administered into organism. Ex vivo technique will allow cells to be selected, analyzed, and cells used for therapy would be the one that are correctly edited. CRISPR-base therapies will need regulations and guidelines which are constantly reviewed to keep up to this rapid developing technology.
The one of main concerns is safety of therapy and situation when unintended targets cause activations of unwanted genes or their destruction – off-target affect. It is important to detect if there are any off-target affects and to ensure that no detectable germ line modifications occurred.
Regulations has also cover efficacy of treatment or treatments what depends on the strategy of curation. Controlling the CRISPR-Cas9 and its deactivation has to be concerned as well. Animal models and disease model has also be taken into account of legislation as well as manufacturing and administration and storage of product.
There is a question if patient will be treated only in specialized centers and they will have to travel globally to those centers to receive treatment. This part is an advantage for shipping section and manufacturers as the travel time and sites amount will be minimized for product delivery.
The FDA has discussed CRISPR-Cas9 technology regulation and they are collaborating with the National Academies of Science and stated that the cross-border regulation of such treatments seems unlikely. Clinical Trial Application and protocol will be reviewed by IRB/IEC and they will request RAC public review as an impact of this is extension of timeline for evaluation of application but it will be appropriately overseen and checked if the trial meet certain criteria.
In EU gene therapy studies has built-in additional time for reviewed in the EU Directive and it also consist additional experts review. GMO use has to be taken into account because it requires authorization for use.
Ten year ago there was no thinking of an technology that will allow the alternation of human genome. Now we can have an impact on human evolution.
See ‘Epigenetics vs. gene editing’ presentation in .pptx format, or see only CRISPR mechanism explained. Please watch in full screen mode.