A vote in the House of Commons last week has allowed the UK to become the first country to carry out mitochondrial DNA transfer in order to replace defective mitochondria in otherwise healthy women’s eggs. Arguments against this procedure included people believing that allowing the transfer of mitochondria would pave the way to the development of ‘designer babies’.
This may surprise some, but the technology to produce a ‘designer’ baby does, in fact, exist. There are currently three different procedures that can be used to edit specific genes in the genome and in some cases replace them with different strands of DNA, potentially altering genetic features. These procedures have been around since the early 2000’s but in the last few years, new procedures have been developed that allow specific genes to be targeted which more efficiency. The two procedures I’m going to discuss are CRISP technology and TALEN’s.
The first procedure I’ll discuss is TALEN’s – transcription activator-like effector nucleases. These contain a non-specific nuclease fused to a sequence specific DNA binding domain that can be altered. These, as in the CRISPR mechanism causes DSB in the genome which are then repaired allowing sequence alteration. TALEN’s are made from TALE’s that are encoded by Xanthomanas app. The DNA binding site of the TALE uses 33-35 amino acid repeats and individual repeats bind to a single base. The base that they bind to is decided by two hypervariable regions which are at positions 12 and 13 and are in the major groove. The number of repeats is proportional to the length of the target site. There is a thymine base at the 5’ end of the base that the first repeat binds to that is highly conserved. Residues at positions 8 and 12 are thought to be for stability and provide this by interacting with each other. There are 4 different hypervariable residues that are usually used and these are: NN (which recognizes guanine), NI (which recognizes adenine), HD (which recognizes cytosine) and NG (which recognizes thymine). On the C-terminal end of the TALE, there is the non-specific nuclease and FokI is most commonly used. TALEN’s have been used successfully in vitro to alter genetic defects for disease such as sickle cell anaemia.
CRISPR stands for clustered regularly interspaced short palindromic repeats and they are usually associated with Cas proteins. CRISPR/Cas technology was first discovered in bacteria as it is a prokaryotic immune defence mechanism. In 2012, it was used to edit genomes of various organisms and in 2014; it was used to cure a specific type of liver disease in mice. The CRISPR system uses Cas 9 which is an endonuclease that uses an RNA guide to cause a double stranded DNA break (DSB) at a specific location. The DSB stimulates the genome to repair the break by one of two pathways; non-homologous end joining or homologous recombination. Non-homologous end joining allows insertions or deletions to occur whereas homologous recombination which allows a specific sequence to be altered. Both these pathways can lead to a change in the genotype and/or phenotype.
These procedures are relatively new and whilst there is a long way to go before it is deemed safe, the trials carried out have been successful. Designer babies may not be as far off as we think…
CRISPR in the Lab. (n.d.). Retrieved February 2014, from Addgene: https://www.addgene.org/CRISPR/guide/
Joung, J., & Sander, J. (2013). TALENs: a widely approachable technology for targeted genome editing. Nature Reviews Molecular Cell Biology , 49-55.
Platt, R., Chen, S., Zhou, Y., Yim, M., Sharp, P., & Zhang, F. (2014). CRISPR-Cas9 Knockin Mice for Genome Editing and Cancer Modeling. Cell , 440-455.