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Gene Editing for Research and Therapy
The research focus of the Harrison Lab is the development of gene editing to study and potentially treat genetic disorders such as cystic fibrosis (CF), cystinosis and atopic dermatitis.
What is CRISPR gene editing?
CRISPR gene editing is a technique that enables the sequence of DNA of a living cell to be precisely changed, and has at least three major biomedical applications:
Editing a DNA sequence is somewhat similar to editing a text document on a computer:
The Gene Editor's Keyboard![]()
https://twitter.com/P_T_Harrison/status/909809309609005056
When was gene editing discovered
Gene editing technology was first described in the early 1980s. The development of this technique (usually referred to as gene targeting at that time) and its subsequent use to study physiological and disease processes, led to the award of the Nobel Prize for Physiology or Medicine in 2007:
https://www.nobelprize.org/nobel_prizes/medicine/laureates/2007
Despite this technology, efficient editing in human cells wasn’t described until 2005 following the development of a synthetic type of proteins known as programmable zinc finger nucleases (ZFNs). The ZFNs enabled researchers to optimise the first step of gene editing, a targeted break in the DNA close to the target region of the gene to be modified.
A couple of years later, a second gene editing system was reported, the Tal-effector nucleases (TALENs) and cells edited with these reagents were approved for use by the US FDA on 30th August 2017 in the treatment of a very specific type of cancer known as B-cell Acute Lymphoblastic Leukaemia:
https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm574058.htm
Despite the availability of these two techniques, it wasn’t until 2012 and the first publication on CRISPR gene editing that the field became to a much wider audience, including our own lab.
How are we using CRISPR to understand Cystic Fibrosis?
We have used both ZFN and CRISPR to correct the DNA sequence in cells which contains the most common CF mutation known as F508del (or p.Phe508del). Many other groups have also used CRISPR, TALENs and other reagents to do similar experiments. Whilst these experiments establish “proof-of-principle” for correction of CF-causing mutations, a common challenge is the relatively low level of editing cells, typically 1-2%, which is regarded as insufficient for therapeutic benefit; the precise level of editing required to treat lung disease in a person with CF is not yet known, but 20-30% is possibly a realistic goal.
Another challenge is that there are at least 281 known CF-causing mutations (see www.cftr2.org), but HDR typically repairs just one mutation at a time. To address efficiency, we have used a simpler approach known as NHEJ to edit a small group of CF-causing mutations known as deep intronic mutations. There are at least five different types of this mutation, and we’ve recently established proof-of-principle for correction of three of them:
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0184009
Whilst our experiments have shown this approach is much more efficient than HDR which we used in our early experiments, this approach will still only correct a small number of disease-causing mutations. Thus, we are now focusing much of our efforts on an approach known as HITI to correct many different mutations at the same time. The HITI technique was only described for the first time in November 2016, but we’ve very recently secured funds from the CF Foundation and the CF Trust to start some experiments using this approach for CF mutations.
Optimisation of editing is just the start of the journey in the development of a new therapeutic approach to CF. Subsequent steps will include the safe and efficient delivery of the editing machinery to ultimately determine if gene editing technology can be used to successfully treat CF lung disease for every person with CF, regardless of their CFTR mutations.
Review Articles
European Biopharmaceutical Review (Autumn 2016)
http://www.samedanltd.com/magazine/12/issue/260/article/4436
Paediatric Pulmonology (Oct 2016)
https://www.ncbi.nlm.nih.gov/pubmed/27662105
Human Genetics (Sept 2016)
https://www.ncbi.nlm.nih.gov/pubmed/27325484
Irish Times (Feb 2016)
http://www.irishtimes.com/news/science/gene-editing-where-do-you-draw-the-line-1.2511209
Biography
What is CRISPR gene editing?
CRISPR gene editing is a technique that enables the sequence of DNA of a living cell to be precisely changed, and has at least three major biomedical applications:
- First, this ability to precisely change a DNA sequence within a cell allows researchers to learn how particular DNA sequences control the normal structure and functions of individual cells.
- Second, it enables us to learn of how certain mutations in the DNA sequence, either acquired or inherited, can cause more than 100 different types of cancer or over 7,000 genetic disorders.
- Third, gene editing could be developed as the basis for a potential treatments for many of these diseases, such as cystic fibrosis (CF), sickle-cell anaemia and cystinosis.
Editing a DNA sequence is somewhat similar to editing a text document on a computer:
- The first step is to find (ctrl F) the precise DNA sequence to be changed then to cut it out (ctrl X). With CRISPR gene editing, a guide RNA molecule in combination with the Cas9 nuclease is used to find the target sequence and cut the DNA at that point.
- The next step in text editing is to copy (ctrl C) a few letters or a word from a dictionary and paste (ctrl V) them into the correct place to change the meaning of a sentence. In cells, we don’t use a dictionary, rather a synthetic piece of DNA with the desired sequence is inserted into the target cells.
- The synthetic DNA contains the new DNA sequences as well as some sequence similarity (or homology) to the target region of the selected gene which helps it to be correctly copied and pasted (or ligated) into the cut site generated by Cas9/guideRNA. The end result is genomic DNA with a sequence corresponding to that in the synthetic DNA.
- In summary, the Cas9/guide RNA makes a targeted break in the genome, and the synthetic DNA provides the new information. The process is mediated in cells by a naturally occurring DNA repair mechanism known as homology-directed repair (HDR).
The Gene Editor's Keyboard
https://twitter.com/P_T_Harrison/status/909809309609005056
When was gene editing discovered
Gene editing technology was first described in the early 1980s. The development of this technique (usually referred to as gene targeting at that time) and its subsequent use to study physiological and disease processes, led to the award of the Nobel Prize for Physiology or Medicine in 2007:
https://www.nobelprize.org/nobel_prizes/medicine/laureates/2007
Despite this technology, efficient editing in human cells wasn’t described until 2005 following the development of a synthetic type of proteins known as programmable zinc finger nucleases (ZFNs). The ZFNs enabled researchers to optimise the first step of gene editing, a targeted break in the DNA close to the target region of the gene to be modified.
A couple of years later, a second gene editing system was reported, the Tal-effector nucleases (TALENs) and cells edited with these reagents were approved for use by the US FDA on 30th August 2017 in the treatment of a very specific type of cancer known as B-cell Acute Lymphoblastic Leukaemia:
https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm574058.htm
Despite the availability of these two techniques, it wasn’t until 2012 and the first publication on CRISPR gene editing that the field became to a much wider audience, including our own lab.
How are we using CRISPR to understand Cystic Fibrosis?
We have used both ZFN and CRISPR to correct the DNA sequence in cells which contains the most common CF mutation known as F508del (or p.Phe508del). Many other groups have also used CRISPR, TALENs and other reagents to do similar experiments. Whilst these experiments establish “proof-of-principle” for correction of CF-causing mutations, a common challenge is the relatively low level of editing cells, typically 1-2%, which is regarded as insufficient for therapeutic benefit; the precise level of editing required to treat lung disease in a person with CF is not yet known, but 20-30% is possibly a realistic goal.
Another challenge is that there are at least 281 known CF-causing mutations (see www.cftr2.org), but HDR typically repairs just one mutation at a time. To address efficiency, we have used a simpler approach known as NHEJ to edit a small group of CF-causing mutations known as deep intronic mutations. There are at least five different types of this mutation, and we’ve recently established proof-of-principle for correction of three of them:
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0184009
Whilst our experiments have shown this approach is much more efficient than HDR which we used in our early experiments, this approach will still only correct a small number of disease-causing mutations. Thus, we are now focusing much of our efforts on an approach known as HITI to correct many different mutations at the same time. The HITI technique was only described for the first time in November 2016, but we’ve very recently secured funds from the CF Foundation and the CF Trust to start some experiments using this approach for CF mutations.
Optimisation of editing is just the start of the journey in the development of a new therapeutic approach to CF. Subsequent steps will include the safe and efficient delivery of the editing machinery to ultimately determine if gene editing technology can be used to successfully treat CF lung disease for every person with CF, regardless of their CFTR mutations.
Review Articles
European Biopharmaceutical Review (Autumn 2016)
http://www.samedanltd.com/magazine/12/issue/260/article/4436
Paediatric Pulmonology (Oct 2016)
https://www.ncbi.nlm.nih.gov/pubmed/27662105
Human Genetics (Sept 2016)
https://www.ncbi.nlm.nih.gov/pubmed/27325484
Irish Times (Feb 2016)
http://www.irishtimes.com/news/science/gene-editing-where-do-you-draw-the-line-1.2511209
Research Interests
Gene Repair
The research focus of the Harrison Lab is the development of gene editing to repair disease-causing mutations in the human genome. The current focus is the use of CRISPR gene editing as research tools and potential therapeutic agents for genetic diseases including Cystic Fibrosis, Cystinosis, and Atopic Dermatitis.
2017 onwards - CRISPR NHEJ and HITI for Cystic Fibrosis and Atopic Dermatitis
The current focus is on NHEJ based methods. Our most recent published study showed effective excision of CF-causing deep intronic mutations (Sanz et al., 2017), but the major focus now is the use of HITI to correct multiple mutations with a single donor and Cas9/gRNA combination. This work is supported by grants from CF Foundation Therapeutics (USA) and CF Trust (UK). The lab is also a member of the CF Trust's Strategic Research Centre for Gene Editing.
We have set up two new collaborations, one with Dusko Ilic in King's College London to edit iPS cells to study atopic dermatitis (funded by the LEO foundation) and with Carlos Farinha in Lisbon to create novel cell lines to study rare CF mutations (part funded by CF Foundation).
2013 to 2016 - CRISPR HDR for Cystic Fibrosis
In 2013, the lab starting using the CRISPR Cas9/gRNA system for gene editing to correct the F508del mutation by HDR (Hollywood et al., 2016) with grants from CF Foundation Therapeutics (USA) and CF Trust (UK).
The lab has funded collaborative projects with Alan Davidson and Jennifer Hollywood in Auckland (funded by Cystinosis Ireland and Health Research Board), and Isabelle Sermet in Paris (funded by HRB).
2005 to 2012 - Application of ZFN HDR to cystic fibrosis
Since 2005, my lab has been working on the production of ZFNs to target the most common gene defect in patients with cystic fibrosis. This work was started by a PhD student, Rowan Flynn, and is currently under further investigation by Ciaran Lee and Jennifer Hollywoord. Using an in vitro system, we developed ZFNs which can target and correct the F508del mutation in the cftr gene http://online.liebertpub.com/doi/abs/10.1089/biores.2012.0218
2008 to 2012 - Application of ZFN HDR to cystinosis
Cystinosis is a rare genetic disorder affecting less than 10 individuals in Ireland. The disease which is a multisystem disorder invariably leads to kidney failure. The gene defect was characterised in 1999, and Dr. Harrison and Dr. Scallan were recently been awarded funding from Cystinosis Ireland (www.cystinosis.ie) and the HRB (www.hrb.ie), as well as the Cystinosis Research Foundation (www.natalieswish.org) to study the applicability of ZFN HDR technology, virus vector delivery and Tale nuclease gene repair. This work has been conducted by Katrin Kaschig and Ciaran Lee.
Between 2001 and 2007, the Department hosted five 10-day residential workshop to provide training for physiologists in molecular biological techniques (Harrison, 2004). The workshop was sponsored by the Physiological Society and the Wellcome Trust, and offered training in experimental procedures in molecular physiology, including the handling of DNA and RNA, sub-cloning, restriction enzyme digests, the use of siRNA technology, western blots, RT-PCR, site-directed mutagenesis and transfection techniques. During this time over 80 physiologists at PhD or post-doctoral level attended these workshops. Further details of other courses organised by the physiological society can be found at www.physoc.org. In 2010, the Department hosted two shorter workshops for physiologists, again sponsored by the Physiological Society.
Research Grants
| Project | Funding Body | Start Date | End Date | Award | |
|---|---|---|---|---|---|
| Science Foundation of Ireland | 01-FEB-16 | 31-JUL-16 | €3,000.00 | ||
| Splicing mutations | Foreign Research Institute | 17-NOV-14 | 16-NOV-16 | €53,476.00 | |
| Modelling cystinosis with human stem cells and the therapeutic potential of aspartic acid | Health Research Board | 01-NOV-14 | 30-OCT-17 | €295,000.00 | |
| Cystic Fibrosis Foundation Therapeutics CRISPR Knock-Out of Class 1 CF Splicing Mutations. | Foreign Research Institute | 01-OCT-14 | 30-SEP-17 | €162,902.00 | |
| Permanent correction of 80% of Disease causing Mutations in Human CF cells. | Foreign Research Institute | 01-OCT-13 | 30-SEP-14 | €59,000.00 | |
| Cystinosis Ireland "In viro gene repair - towards a cure for cystinosis. | Irish Funded Research | 01-JUN-13 | 31-MAY-14 | €10,000.00 | |
| Gene repair Conference. | Health Research Board | 01-DEC-12 | 30-JUN-14 | €14,000.00 |
Publications
Peer Reviewed Journals
| Year | Publication | |
|---|---|---|
| (2016) | 'Analysis of gene repair tracts from Cas9/gRNA double-stranded breaks in the human CFTR gene' Hollywood, JA,Lee, CM,Scallan, MF,Harrison, PT (2016) 'Analysis of gene repair tracts from Cas9/gRNA double-stranded breaks in the human CFTR gene'. Scientific Reports, 6 [DOI] [Details] | |
| (2016) | 'Genetic medicines for CF: Hype versus reality' Alton EW;Boyd AC;Davies JC;Gill DR;Griesenbach U;Harrison PT;Henig N;Higgins T;Hyde SC;Innes JA;Korman MS; (2016) 'Genetic medicines for CF: Hype versus reality'. Pediatric Pulmonology, 51 (S44) [DOI] [Details] | |
| (2016) | 'Impact of gene editing on the study of cystic fibrosis' Harrison PT;Sanz DJ;Hollywood JA; (2016) 'Impact of gene editing on the study of cystic fibrosis'. Human Genetics, 135 (9) [DOI] [Details] | |
| (2012) | 'Correction of the ΔF508 mutation in the CFTR gene by zinc finger nuclease homology-directed repair' Lee, CM, Flynn, R, Hollywood, JA, Scallan, MF and Harrison, PT (2012) 'Correction of the ΔF508 mutation in the CFTR gene by zinc finger nuclease homology-directed repair'. BioResearch Open Access, 1 (2):99-108 [DOI] [Details] | |
| (2011) | 'E47 retroviral rescue of intrinsic B cell defects in senescent mice' Landin, Ana Marie,Frasca, Daniela,Harrison, Patrick,Scallan, Martina,Riley, Richard L.,Blomberg, Bonnie B.; (2011) 'E47 retroviral rescue of intrinsic B cell defects in senescent mice'. Aging Cell, [Details] | |
| (2010) | 'AAV2-mediated in vivo immune gene therapy of solid tumours' Collins, S. A.,Buhles, A.,Scallan, M. F.,Harrison, P. T.,O'Hanlon, D. M.,O'Sullivan, G. C.,Tangney, M.; (2010) 'AAV2-mediated in vivo immune gene therapy of solid tumours'. Genetic vaccines and therapy, 8 [Details] | |
| (2010) | 'Effects of GDF5 overexpression on embryonic rat dopaminergic neurones in vitro and in vivo' O’Sullivan, D.B., Harrison, P.T., Sullivan, A.M. (2010) 'Effects of GDF5 overexpression on embryonic rat dopaminergic neurones in vitro and in vivo'. Journal of Neural Transmission, 117 (5):559-572 [DOI] [Details] | |
| (2008) | 'Application of Gene Therapy in Diabetes Care (review)' Harrison PT ; (2008) 'Application of Gene Therapy in Diabetes Care (review)'. Infect Disord Drug Targets, 8 (2):129-133 [Details] | |
| (2008) | 'Viral vectors in cancer immunotherapy: which vector for which strategy?' Collins SA, Guinn BA, Harrison PT, Scallan MF, O'Sullivan GC, Tangney M; (2008) 'Viral vectors in cancer immunotherapy: which vector for which strategy?'. Current Gene Therapy, 8 (2):66-78 [Details] | |
| (2004) | 'FcgammaRIIa expression with FcgammaRI results in C-reactive protein- and IgG-mediated phagocytosis. J Leukoc Biol' Bodman-Smith, K. B.,Gregory, R. E.,Harrison, P. T.,Raynes, J. G.; (2004) 'FcgammaRIIa expression with FcgammaRI results in C-reactive protein- and IgG-mediated phagocytosis. J Leukoc Biol'. J Leukoc Biol, 75 (6):1029-35 [Details] | |
| (2002) | 'C-reactive protein-mediated phagocytosis and phospholipase D signalling through the high-affinity receptor for immunoglobulin G (FcgammaRI). Immunology' Bodman-Smith, K. B.,Melendez, A. J.,Campbell, I.,Harrison, P. T.,Allen, J. M.,Raynes, J. G.; (2002) 'C-reactive protein-mediated phagocytosis and phospholipase D signalling through the high-affinity receptor for immunoglobulin G (FcgammaRI). Immunology'. Immunology, 107 (2):252-60 [Details] | |
| (1999) | 'Novel cell lines for the analysis of preprotachykinin A gene expression identify a repressor domain 3' of the major transcriptional start site' Fiskerstrand CE, Newey P, Ebrahimi B, Gerrard L, Harrison P, McGregor GP, Quinn JP; (1999) 'Novel cell lines for the analysis of preprotachykinin A gene expression identify a repressor domain 3' of the major transcriptional start site'. The Biochemical Journal, 341 ( Pt 3) :847-852 [Details] | |
| (1999) | 'Neuronal-specific and nerve growth factor-inducible expression directed by the preprotachykinin-A promoter delivered by an adeno-associated virus vector. Neuroscience' Harrison, P. T.,Dalziel, R. G.,Ditchfield, N. A.,Quinn, J. P.; (1999) 'Neuronal-specific and nerve growth factor-inducible expression directed by the preprotachykinin-A promoter delivered by an adeno-associated virus vector. Neuroscience'. Neuroscience, 94 (3):997-1003 [Details] | |
| (1998) | 'High affinity IgG binding by FcgammaRI (CD64) is modulated by two distinct IgSF domains and the transmembrane domain of the receptor. Protein Eng' Harrison, P. T.,Allen, J. M.; (1998) 'High affinity IgG binding by FcgammaRI (CD64) is modulated by two distinct IgSF domains and the transmembrane domain of the receptor. Protein Eng'. Protein Eng, 11 (3):225-32 [Details] | |
| (1998) | 'Use of GPI-anchored proteins to study biomolecular interactions by surface plasmon resonance. FEBS Lett' Harrison, P. T.,Campbell, I. W.,Allen, J. M.; (1998) 'Use of GPI-anchored proteins to study biomolecular interactions by surface plasmon resonance. FEBS Lett'. FEBS Lett, 422 (3):301-6 [Details] | |
| (1998) | 'Lysosomal routing of Fc gamma RI from early endosomes requires recruitment of tyrosine kinases. Immunology' Norman, J. C.,Harrison, P. T.,Davis, W.,Floto, R. A.,Allen, J. M.; (1998) 'Lysosomal routing of Fc gamma RI from early endosomes requires recruitment of tyrosine kinases. Immunology'. Immunology, 94 (1):48-55 [Details] | |
| (1996) | 'Protein:protein interactions in the lipid bilayer (review)' Harrison PT. ; (1996) 'Protein:protein interactions in the lipid bilayer (review)'. Mol Membr Biol, 13 (`2):67-79 [Details] | |
| (1995) | 'Two distinct regions of FC gamma RI initiate separate signalling pathways involved in endocytosis and phagocytosis. EMBO J' Davis, W.,Harrison, P. T.,Hutchinson, M. J.,Allen, J. M.; (1995) 'Two distinct regions of FC gamma RI initiate separate signalling pathways involved in endocytosis and phagocytosis. EMBO J'. EMBO J, 14 (3):432-41 [Details] | |
| (1995) | 'The interaction between human Fc gamma RI and the gamma-chain is mediated solely via the 21 amino acid transmembrane domain of Fc gamma RI. Mol Membr Biol' Harrison, P. T.,Bjorkhaug, L.,Hutchinson, M. J.,Allen, J. M.; (1995) 'The interaction between human Fc gamma RI and the gamma-chain is mediated solely via the 21 amino acid transmembrane domain of Fc gamma RI. Mol Membr Biol'. Mol Membr Biol, 12 (4):309-12 [Details] | |
| (1995) | 'Site-directed mutagenesis of varicella-zoster virus thymidylate synthase. Analysis of two highly conserved regions of the enzyme. Eur J Biochem' Harrison, P. T.,Scott, J. E.,Hutchinson, M. J.,Thompson, R.; (1995) 'Site-directed mutagenesis of varicella-zoster virus thymidylate synthase. Analysis of two highly conserved regions of the enzyme. Eur J Biochem'. Eur J Biochem, 230 (2):511-6 [Details] | |
| (1995) | 'Fc gamma receptor-mediated phagocytosis requires tyrosine kinase activity and is ligand independent. Eur J Immunol' Hutchinson, M. J.,Harrison, P. T.,Floto, R. A.,Allen, J. M.; (1995) 'Fc gamma receptor-mediated phagocytosis requires tyrosine kinase activity and is ligand independent. Eur J Immunol'. Eur J Immunol, 25 (2):481-7 [Details] | |
| (1994) | 'Binding of monomeric immunoglobulin G triggers Fc gamma RI-mediated endocytosis. J Biol Chem' Harrison, P. T.,Davis, W.,Norman, J. C.,Hockaday, A. R.,Allen, J. M.; (1994) 'Binding of monomeric immunoglobulin G triggers Fc gamma RI-mediated endocytosis. J Biol Chem'. J Biol Chem, 269 (39):24396-402 [Details] | |
| (1994) | 'A convenient method for the construction and expression of GPI-anchored proteins. Nucleic Acids Res' Harrison, P. T.,Hutchinson, M. J.,Allen, J. M.; (1994) 'A convenient method for the construction and expression of GPI-anchored proteins. Nucleic Acids Res'. Nucleic Acids Res, 22 (18):3813-4 [Details] | |
| (1991) | 'Evolution of herpesvirus thymidine kinases from cellular deoxycytidine kinase. J Gen Virol' Harrison, P. T.,Thompson, R.,Davison, A. J.; (1991) 'Evolution of herpesvirus thymidine kinases from cellular deoxycytidine kinase. J Gen Virol'. J Gen Virol, 72 ( Pt 10) :2583-6 [Details] |
Conference Publications
| Year | Publication | |
|---|---|---|
| (2014) | 11th European Cystic Fibrosis Society Meeting, Malta Hollywood, JA, Lee, CM, Scallan, MF and Harrison, PT. (2014) Strategy to correct >80% of CF-causing mutations using CRISPR/Cas9 and mini-gene constructs 11th European Cystic Fibrosis Society Meeting, Malta [Details] | |
| (2007) | 15th Annual Congress of the European Society of Gene and Cell Therapy Collins S., Harrison PT, Scallan MF; (2007) Adeno-associated virus-mediated gene therapy for cancer . In: Human Gene Therapy 18 (10) eds. 15th Annual Congress of the European Society of Gene and Cell Therapy , pp.999-999 [Details] | |
| (2005) | Viral vectors to deliver neurotrophin genes to a rat model of Parkinson's disease Kelly, TA, Harrison, PT, Scallan, MF and Sullivan, AM; (2005) Viral vectors to deliver neurotrophin genes to a rat model of Parkinson's disease Viral vectors to deliver neurotrophin genes to a rat model of Parkinson's disease , pp.529-530 [Details] | |
| (2005) | 16th International Congress on Parkinson’s Disease and Related Disorders, Berlin, Germany Kelly, T.A., Harrison, P.T., Scallan, M.F., Sullivan, A.M. (2005) Lentiviral-mediated delivery of growth/differentiation factor-5 attenuates parkinsonian symptoms in the rat . In: Parkinsonism & Related Disorders Volume 11, Supplement 2 eds. 16th International Congress on Parkinson’s Disease and Related Disorders, Berlin, Germany Berlin, [Details] | |
| (2005) | Physiological Society meeting, Bristol, UK Flynn R, O’Sullivan D, Sullivan, A.M., Harrison P. (2005) Use of pCEP4 Vector for Simple and Rapid Establishment of Stable Cell-Lines and Long-Term Gene Expression Physiological Society meeting, Bristol, UK [Details] | |
| (2005) | Society for Neuroscience meeting, Washington, USA O’Sullivan, D.B., Harrison, P.T., Nolan, Y.M., Sullivan, A.M. (2005) Prevention of apoptosis in cultured dopaminergic neurons by GDNF and GDF5 . In: Soc. Neurosci. Abs. 899.12 eds. Society for Neuroscience meeting, Washington, USA Washington DC, USA, , 12-NOV-05 - 16-NOV-05 , pp.889.12-* [Details] | |
| (2004) | Anatomical Society of Great Britain and Ireland Summer Meeting 2004, Cork, Ireland O’Sullivan, D.B., Harrison, P.T., Sullivan, A.M. (2004) Rat ventral mesencephalic cultures transfected with a plasmid expressing growth/differentiation factor 5 exhibit improved dopaminergic neuronal survival . In: J. Anat. 205 (6) eds. Anatomical Society of Great Britain and Ireland Summer Meeting 2004, Cork, Ireland [Details] | |
| (2004) | Physiological Society meeting, Bristol, UK Kelly T.A., Harrison P.T., Scallan M.F., Sullivan, A.M. (2004) Viral vectors to deliver neurotrophin genes to a rat model of Parkinson’s disease Physiological Society meeting, Bristol, UK [Details] | |
| (2004) | 4th Forum of European Neuroscience Lisbon Portugal O’Sullivan, D.B., Sullivan, A.M., Harrison, P.T. (2004) Establishment of neurotrophin-expressing dopaminergic cells for transplantation in Parkinson’s disease . In: FENS Abstr. Vol.2, A053.17 eds. 4th Forum of European Neuroscience Lisbon Portugal [Details] | |
| (2004) | Anatomical Society of Great Britain and Ireland Summer Meeting 2004, Cork, Ireland Kelly, T.A., Harrison, P.T., Scallan, M.F., Sullivan, A.M. (2004) Viral vectors to deliver neurotrophin genes to a rat model of Parkinson’s disease . In: J. Anat. 205 (6) eds. Anatomical Society of Great Britain and Ireland Summer Meeting 2004, Cork, Ireland [Details] | |
| (2013) | 22nd European Gene and Cell Therapy Conference, Madrid, Spain Hollywood, JA, Lee, CM1, Kaschig, K., Artemiuk, P., Scallan, MF and Harrison, PT. (2013) Gene editing of CFTR and CTNS mutations using ZFNs and CRISPr/Cas-9 guide RNAs 22nd European Gene and Cell Therapy Conference, Madrid, Spain [Details] | |
| (2013) | Gene editing of CFTR and CTNS mutations using ZFNs and CRISPr/Cas-9 guide RNAs Hollywood, JA,Lee, CM,Kaschig, K,Flynn, R,Artemiuk, P,Scallan, MF,Harrison, PT (2013) HUMAN GENE THERAPY Gene editing of CFTR and CTNS mutations using ZFNs and CRISPr/Cas-9 guide RNAs , pp.87-87 [Details] | |
| (2011) | European Society of Gene and Cell Therapy, Brighton UK Lee, CM,Scallan, MF,Harrison, PT (2011) The development of zinc finger nucleases to target mutations in the cystinosin gene using the rapid OPEN screening method European Society of Gene and Cell Therapy, Brighton UK [Details] | |
| (2011) | European Society of Gene and Cell Therapy, Brighton UK Kaschig, K,Lee, CM,Hollywood, JA,Scallan, MF,Harrison, PT (2011) Kaschig, K,Lee, CM,Hollywood, JA,Scallan, MF,Harrison, PT European Society of Gene and Cell Therapy, Brighton UK [Details] | |
| (2011) | Cystinosis gene repair: A functional assay to detect restoration of the CTNS gene via homology-directed repair using Zinc finger nucleases Kaschig, K,Lee, CM,Hollywood, JA,Scallan, MF,Harrison, PT (2011) HUMAN GENE THERAPY Cystinosis gene repair: A functional assay to detect restoration of the CTNS gene via homology-directed repair using Zinc finger nucleases , pp.49-49 [Details] | |
| (2011) | The development of zinc finger nucleases to target mutations in the cystinosin gene using the rapid OPEN screening method Lee, CM,Scallan, MF,Harrison, PT (2011) HUMAN GENE THERAPY The development of zinc finger nucleases to target mutations in the cystinosin gene using the rapid OPEN screening method , pp.50-50 [Details] |
Book Chapters
| Year | Publication | |
|---|---|---|
| (2011) | 'Comparison of DNA Delivery and Expression Using Frequently Used Delivery Methods' Collins SA, Morrissey D, Rajendran S, Casey G, Scallan MF, Harrison PT, O'Sullivan GC, Tangney M. ; (2011) 'Comparison of DNA Delivery and Expression Using Frequently Used Delivery Methods' In: Gene Therapy - developments and future perspectives. Croatia: InTech. [Details] | |
| (2009) | 'Gene Therapy and Individualised Medicine' Harrison, PT, Flynn, R, Lee CM ; (2009) 'Gene Therapy and Individualised Medicine' In: Predictive Diagnostics and Personalized Treatment. Nova Science Publishers, Inc. [Details] |
Professional Activities
Professional Associations
| Association | Function | From / To | |
|---|---|---|---|
| European Association of Predictive, Preventive and Personalised Medicine (EPMA; www.epmanet.eu) | Ireland’s representative for EPMA (2008-2010) | 01-JAN-08 / 31-DEC-10 | |
| Physiological Society - Member | Member since 2000 | 01-JAN-00 / | |
| Physiological Society | Finance Committee Member | 01-JAN-02 / 31-DEC-05 | |
| Physiological Society | Council Member and Trustee | 01-JAN-04 / 31-DEC-06 | |
| Ligand Xpress (SC177459) | Company Director | 01-JUL-98 / 31-DEC-00 |
Conference Contributions
| Year | Publication | |
|---|---|---|
| (2016) | Physiological Society Gene Editing Workshop, Harrison PT (2016) Beginners guide to Cpf1 and Cas9 Gene Editing. [Invited Lectures (Workshops)], Physiological Society Gene Editing Workshop, London, UK , 15-NOV-16. [Details] | |
| (2016) | Association of Clinical Biochemists Ireland, Harrison, PT (2016) Z to A of Gene Editing. [Invited Lectures (Conference)], Association of Clinical Biochemists Ireland, Cork, Ireland , 11-NOV-16. [Details] | |
| (2016) | NACFC, Harrison, PT (2016) CF Deep Intron Theratype Gene Editing. [Invited Lectures (Workshops)], NACFC, Orlando . [Details] | |
| (2016) | CFF: New Froniters, Patrick Harrison (2016) Gene Editing for CF Therapy. [Chair Sessions at Symposia], CFF: New Froniters, Savannah, USA . [Details] | |
| (2016) | 39th ECFS, Patrick Harrison (2016) Novel Models for CF Gene Editing. [Invited Lectures (Conference)], 39th ECFS, Basel, Switzerland . [Details] | |
| (2016) | 2nd Genetic Disorders UK, Patrick Harrison (2016) Gene Editing, Cut, Correct, Cure?. [Keynote Speaker], 2nd Genetic Disorders UK, London, UK . [Details] | |
| (2016) | 2nd Dublin Cystinosis Workshop, Patrick Harrison (2016) Conference Organiser. [Conference Organising Committee Chairperson], 2nd Dublin Cystinosis Workshop, Dublin, Ireland . [Details] | |
| (2016) | 2nd Dublin Cystinosis Workshop, Patrick Harrison (2016) Gene Replacement Therapy for Cystinosis. [Invited Lectures (Conference)], 2nd Dublin Cystinosis Workshop, Dublin, Ireland . [Details] | |
| (2016) | Austrian Dermatological Society, Patrick Harrison (2016) Cas9 gene editing for Skin disorders. [Invited Lectures (Conference)], Austrian Dermatological Society, Salzburg, Austria . [Details] | |
| (2015) | Oxford Global Gene Editing Conference, Patrick Harrison (2015) Cas9 gene editing for CF. [Invited Lectures (Conference)], Oxford Global Gene Editing Conference, London, UK . [Details] | |
| (2015) | North American CF Conference, Patrick Harrison (2015) Gene Editing Workshop. [Invited Lectures (Conference)], North American CF Conference, Phoenix USA , 28-OCT-15. [Details] | |
| (2015) | British Society of Gene and Cell Therapy, Patrick Harrison (2015) CRISPR gene editing in metabolic disease. [Invited Lectures (Conference)], British Society of Gene and Cell Therapy, Glasgow, UK . [Details] | |
| (2015) | CFF: Pushing the Frontiers, Patrick Harrison (2015) CRISPR gene KO for type I splicing mutations. [Invited Lectures (Conference)], CFF: Pushing the Frontiers, Washington DC, USA . [Details] | |
| (2014) | 1st European Workshop on Cystinosis Research, Harrison, PT (2014) Workshop. [Conference Organising Committee Chairperson], 1st European Workshop on Cystinosis Research, Dublin . [Details] | |
| (2014) | 11th European Cystic Fibrosis Society Basic Science Conference, Harrison, PT (2014) Symposium co-chair - CF modifier genes. [Chair Sessions at Symposia], 11th European Cystic Fibrosis Society Basic Science Conference, Malta . [Details] | |
| (2014) | 1st European Workshop on Cystinosis Research, Harrison, PT (2014) Invited Speaker - Gene Editing for Cystinosis. [Invited Lectures (Workshops)], 1st European Workshop on Cystinosis Research, Dublin . [Details] | |
| (2012) | 35th European Cystic Fibrosis Conference, Dublin “Overview of Proteins involved in Membrane Trafficking”, Harrison, PT (2012) Invited Speaker - Overview of Proteins involved in Membrane Trafficking. [Invited Lectures (Conference)], 35th European Cystic Fibrosis Conference, Dublin “Overview of Proteins involved in Membrane Trafficking”, Dublin . [Details] | |
| (2012) | 35th European Cystic Fibrosis Society Clinical Conference, Harrison, PT (2012) Symposium co-chair - CF Rescue Strategies. [Chair Sessions at Symposia], 35th European Cystic Fibrosis Society Clinical Conference, Dublin . [Details] |
Other Activities
| Description | |
|---|---|
2014 - PhD External Examiner, Aberdeen | |
2014 - Poster Judge, UK Cystic Fibrosis Conference, Manchester | |
2012 - PhD External Examiner, Liverpool | |
2007 - PhD External Examiner, Cambridge | |
2006 - PhD External Examiner, Liverpool | |
2005 - Poster Judge, Young Physiologists’ Symposium, Physiological Society, Seville | |
2004 - Poster Judge, Physiological Society Conference, Cork |
Committees
| Committee | Function | From / To | |
|---|---|---|---|
| CK402 - Biological Sciences | Member | 2012 / | |
| College of Medicine and Health Executive Committee | Member - representing School of Life Sciences | 2010 / 2011 | |
| Biological Sciences - UCC | 2nd Biological Sciences BSc co-ordination | 2002 / 2009 |
Employment
| Employer | Position | From / To | |
|---|---|---|---|
| University College Cork | Senior Lecturer | 01-OCT-01 / | |
| Cellular Physiology Research Unit, UCC | Senior Research Fellow | 01-NOV-00 / 01-SEP-01 | |
| University of Glasgow | Lecturer | 01-NOV-98 / 01-OCT-00 | |
| University of Edinburgh | Post-Doc | 01-APR-97 / 01-OCT-98 | |
| Institute of Molecular Pathology, VIenna | Post-Doc | 25-MAR-96 / 26-MAR-97 | |
| University of Glasgow | Post-Doc | 01-OCT-94 / 24-MAR-96 | |
| University of Cambridge | Post-Doc | 01-JAN-92 / 30-SEP-94 |
Education
| Year | Institution | Qualification | Subject | |
|---|---|---|---|---|
| 1992 | University of Glasgow | PHD | Virology | |
| 1987 | University of Liverpool | BSC | Biochemistry |
Consultancy
| Client | Description | |
|---|---|---|
| Enterprise Ireland | ||
| Action Medical Research for Children (UK) | ||
| Biological and Biomedical Science Research Council (UK) | ||
| Health Research Board |
Outreach Activities
| Description | |
|---|---|
2010 - Colaiste Choilm School - Seminar Speaker: Gene Delivery – The Science Behind Gene Therapy | |
2008 - Nurture Creche Cork - Kids Workshop Presenter - How do you build a human? | |
2005 - British Association Festival in Dublin - Seminar Speaker: Gene Delivery – The Science Behind Gene Therapy | |
2010 - Nurture Creche Cork - Kids Workshop Presenter - How do you build a human? |
Journal Activities
| Journal | Role | To / From | |
|---|---|---|---|
| Scientific Reports | Referee | - | |
| Journal Of Cystic Fibrosis | Referee | - | |
| Epma Journal | Member of Editorial Board | - | |
| Molecular Therapy | Referee | - |
Languages
| Language | Reading | Writing | Speaking | |
|---|---|---|---|---|
| German | Basic | Basic | Functional | |
| French | Functional | Basic | Functional |
Teaching Activities
Teaching Interests
Recent Postgraduates
| Graduation Year | Student Name | Institution | Degree Type | Thesis Title | |
|---|---|---|---|---|---|
| 2013 | Jennifer Hollywood | PHD | Cystic fibrosis gene repair : correction of ΔF508 using ZFN and CRISPR/Cas9 guide RNA gene editing tools | ||
| 2013 | Katrin Kaschig | PHD | Zinc finger nuclease gene repair as a treatment for cystinosis | ||
| 2013 | Ana Marie Landin | PHD | Molecular regulation of B cell deficiency with age : a study of E47 and Pax-5 | ||
| 2011 | Sarah Collins | PHD | Adeno-Associated virus vectors for cancer gene therapy | ||
| 2010 | Ciaran Lee | UCC | PHD | Cystic fibrosis gene repair : development of zinc finger nucleases for homology directed repair of the CFTR |
Modules Taught
| Term (ID)) | Title | Link | Subject | |
|---|---|---|---|---|
| 2018 | Cell and Epithelial Physiology | PL2025 | Cell and Epithelial Physiology | |
| 2018 | Cell and Epithelial Physiology | PL3005 | Cell and Epithelial Physiology | |
| 2018 | Literature Project on Genetics | GN3002 | Literature Project on Genetics | |
| 2018 | Molecular and Cellular Physiology Techniques | PL6001 | Molecular and Cellular Physiology Techniques |