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• R0075: Improving methods for biopsy and preimplantation diagnosis of inherited genetic disease of human preimplantation embryos
• R0133: Correlation of embryo morphology with ability to generate embryonic stem cell lines and subsequent growth differentiative characteristics

R0075: Improving methods for biopsy and preimplantation diagnosis of inherited genetic disease of human preimplantation embryos

Licence holder: Professor Peter Braude

Preimplantation genetic diagnosis (PGD) is a reproductive option for couples at substantial risk of conceiving a pregnancy affected with a known genetic disease who wish to avoid the emotional burden associated with an affected child, termination of pregnancy or recurrent miscarriages. PGD has been offered as a service at Guy’s and St Thomas’ for over ten years, and it is now the busiest and most successful unit in the country.

PGD has been used for single gene diseases such as cystic fibrosis, for diseases which only affect males by selecting female embryos, and for couples with chromosome rearrangements.  For single gene diseases, one cell is removed from a 3-day old embryo and tested for the mutation. A separate PGD test has to be developed for every different mutation, requiring substantial resources not always available in state-run medicine. In addition, these tests are technically difficult and very sensitive to contamination with non-embryo DNA.

Over the duration of our previous licence, we developed a new technique at Guy’s, Preimplantation Genetic Haplotyping (PGH) which improves the reliability of single cell genetic testing and enables it to be extended to a wide range of diseases. It has also allowed us to move away from sexing embryos as a means of avoiding some genetic disease as we can use PGH to detect and distinguish unaffected males in addition to unaffected or carrier females.

We intend to work over the next three years, further developing this approach for a wider range of genetic disorders, and to see whether we can extend the approach to include tests for some serious or lethal chromosomal trisomies such as Edward, Patau and Down syndrome. Further research will look at effect of mosaicism on diagnosis, and the impact of mitochondrial function during early development.

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R0133: Correlation of embryo morphology with ability to generate embryonic stem cell lines and subsequent growth differentiative characteristics

Licence holder: Professor Peter Braude

Stem cells are unique cell populations which are able to undergo both self renewal and specialisation into new cell types.

Although stem cells have been found in a wide variety of adult tissues, embryonic stem (ES) cells, which have been isolated from the inner cell mass (ICM) of blastocyst stage (Day 5) embryos are thought to maintain a higher potential for specialisation into many different cell types which may be of use in treating some serious degenerative diseases such as Parkinson disease, diabetes, or repair organs following stroke or heart attacks.

In order to achieve this aim, stem cells need to made reliably and safely for use. Not only does this require an assessment of which embryos are more likely to produce stem cell lines and the conditions likely to facilitate stem cell growth, but there is also the requirement for them to be produced under conditions suitable for use in human therapy.

This will require a methodical study of embryo quality and potential of individual cells which make up the early embryo, and also trial and error of conditions that facilitate safe stem cell production. It is also important that any such information gleaned is shared internationally to minimize the number of embryos used. In addition, stem cell lines derived from embryos from patients who have undergone PGD to avoid transmission of serious genetic disease, may be useful in studying mechanisms of how those genetic diseases progress and cause symptoms.

Studies of stem cells derived from embryos carrying clinically-relevant mutations, e.g. with the Huntington’s or cystic fibrosis mutation, will be useful not only in understanding how the mutation affects various tissues, but also in developing molecules which may be used in the treatment or amelioration of symptoms caused by these serious genetic conditions.

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