Niakan lab

Human Embryo and Stem Cell Laboratory

: Human embryo genome editing licence

In February 2016, Dr Kathy Niakan's team became the first to receive permission from the Human Fertilisation and Embryology Authority (HFEA) to use the genome editing technique 'CRISPR-Cas9' in human embryos. The technique will allow her team to better understand the earliest stages of human development.

Genetic modification of human embryos in research has been permitted by the legislation since 2009. The significance of the HFEA licence for this work is that it is the first time genome editing using CRISPR-Cas9, a specific and efficient genome editing technique, has been approved.

The embryos used in the research project are left over from patients' fertility treatment and donated by patients. They are surplus to the patients' treatment or family-building needs, and so would otherwise be disposed of. The embryos will never be used to establish a pregnancy. The research focuses on the first seven days of development after fertilisation, and none of the embryos the team do research on will ever be grown past a maximum of 14 days after fertilisation, in accordance with legislation.

Investigating early development could ultimately lead to improvements in infertility treatment, and a deeper understanding of the earliest stages of human life. It is important to note that these potential improvements in infertility treatment would not be delivered through genome editing: it is illegal to implant an embryo modified in this way into a human. Rather, a better understanding of this stage might allow, for example, the development of more successful human embryo culture conditions within IVF treatment.

Patient information and consent forms

In any research using donated embryos from IVF treatment, it is imperative that those considering donating their embryos can give fully informed consent. This process is carefully regulated. Patient information and consent documents, and any updates to them, are always subject to approval by the relevant ethics committee (in this case, the Cambridge Central Research Ethics Committee). There is also a requirement for the patient information and consent documents to comply with HFEA licence conditions.

Note that:

• In all work of this type, patient information and consent documents are subject to updates. The version is clearly shown on the document.
• Different IVF clinics will use different versions of the documents. In some cases this reflects the style preferences of the particular clinic; in others it reflects the fact that the clinic may be donating embryos to more than one research project and this needs to be reflected on the document. For transparency, all versions of the consent documents for embryos donated to Dr Niakan's research project are provided here. Clinic names may be redacted.
• Patients undergoing fertility treatment would be given the information and consent forms by their clinic, to allow them to consider in an informed way the option of donating surplus embryos.

More about the science

The Niakan laboratory is interested in improving our understanding of how cells become specialised during the earliest stages of human development, within the first week after fertilisation. The first important step in this process is when a small subset of cells are set aside to develop into the foetus, whilst another subset of cells becomes destined to form the placenta. Identifying the genes that are essential for these specialisation processes may provide insight into the causes of pregnancy failures or birth defects. Understanding this important switch in cell fate may also provide a deeper understanding of stem cell formation.

CRISPR-Cas9 has often been described as a pair of molecular scissors, as it allows highly efficient and precise alterations of the DNA sequence. The system has two components: the Cas9 protein that makes the cut in the DNA, and a guide RNA that targets Cas9 to a particular gene region. A break in the DNA sequence triggers repair mechanisms present in all human cells, which attempt to correct the damage; this process can lead to small mutations that might inactivate the gene. Dr Niakan's team introduce the Cas9 protein and guide RNAs into human embryos at the one-cell stage, with the aim of inactivating genes that may be important for early development and investigating their role.

These CRISPR-targeted embryos have their development stopped within seven days of fertilisation and will be analysed to reveal the alterations to the DNA. Some of the embryos may be used to derive human embryonic stem cells, which again is all in vitro (in a petri dish), as some target genes are also crucial for maintaining stem cell function. Several conventional methods are then be used in line with HFEA guidelines to examine gene or protein expression to determine the importance of these target genes in early human development.