Forward thinking to
reverse cell ageing

Developing a new generation of senotherapeutic interventions to target the diseases and aesthetic signs of ageing.

Photo of Astrocyte cells. Senescent primary astrocyte cells.
Image credit: Dr Eva Latorre, Harries Lab.

About Us

SENISCA is a biotech spinout company from the University of Exeter, founded in 2020 and dedicated to the development of new approaches to reverse cellular senescence (senotherapeutics).

Our founders are world leaders in molecular and cellular biology and have patent-protected an innovation for the reversal of cellular senescence. This innovation works by restoring the ability of cells to ‘fine tune’ the expression of their genes to rejuvenate aged cells.

At SENISCA, we are using this knowledge, concerning how and why cells become senescent, to develop a new generation of oligonucleotide-based interventions, to turn back the ageing clock in old cells and to target the diseases and aesthetic signs of ageing.

Photo of fibroblast cells 48 hour timelapse of rejuvenating senescent primary human dermal fibroblast cells.
Image credit: Dr Eva Latorre, Harries Lab.

Scientific Approach

A major cause of age-related diseases and the aesthetic signs of ageing is the accumulation of senescent cells in aged tissues and organs; removal of such cells has been shown to be capable of bringing about ‘rejuvenation’ of function in people and animals. At SENISCA, we have discovered a new and druggable means to reverse senescence through modulation of RNA splicing.

When genes are switched on, they make a message (mRNA), containing the instructions to make whatever the cell requires. Most genes can make more than one type of mRNA message (mRNA isoform), depending on the needs of the cell in a process termed ‘alternative splicing’. The balance of mRNA isoforms made from each gene is critical and underpins the ability of cells to adapt and respond to their environment. This ability to ‘fine tune’ gene outputs is vital for long-term health. The choice of which isoforms are produced is made by a set of regulatory proteins (collectively termed splicing factors).

Our founders have discovered that levels of splicing factors change during ageing, compromising our ability to carry out this ‘fine tuning’ of gene expression. This is a fundamental reason why cells become senescent. Compromised molecular resilience is a major cause of the ill health and frailty that accompanies ageing. We have demonstrated that restoration of splicing factor levels to those seen in younger cells is able to effectively turn back the ageing clock in old cells, bringing about reversal of senescence.

At SENISCA, we are using oligonucleotide-based therapeutic approaches to reset splicing factor levels and reverse senescence. We anticipate that understanding the molecular basis of rejuvenation will highlight new treatments for the diseases and aesthetic aspects of ageing. More importantly, it is likely that preventative approaches based on rejuvenation will be developed reducing both disease incidence and severity.

Photo of Fibroblast cells background First overlay image of Fibroblast cells Second overlay image of Fibroblast cells Proliferating primary human fibroblast cells.
Image credit: Dr Nicola Jeffery, Harries Lab.

The Team

Executive

Photo of Professor Lorna Harries

Professor Lorna Harries

Chief Scientific Officer

Lorna leads the R&D team at SENISCA, targeting age-related changes in alternative splicing as a novel, and druggable, hallmark of ageing. Alongside her CSO role at SENISCA, Lorna holds a personal Chair in Molecular Genetics at the University of Exeter Medical School, where she runs the RNA-mediated Mechanisms of Disease group.

Lorna has authored over 135 peer-reviewed publications in the RNA, Ageing and Senescence space. She is a regular invited and keynote speaker at International conferences and currently acts as Secretary for the British Society for Research on Ageing.

Photo of Dr Ben Lee

Dr Ben Lee

Chief Technical Officer

Ben is SENISCA’s technical lead and laboratory manager.

Before joining SENISCA, Ben was technical specialist for the RNA-mediated Mechanisms of Disease group at the University of Exeter Medical School, where his work in the ageing and alternative splicing field contributed towards the characterisation of RNA regulation as a novel hallmark of ageing.

Ben is author on more than a dozen peer-reviewed publications in the ageing and senescence field and recently completed the Innovate UK-funded ICURe programme.

Photo of Kirsty Semple

Kirsty Semple

Chief Operating Officer

Kirsty is the commercial, finance and investment lead at SENISCA. She is an accomplished Chief Operations Director, with over 20 years experience at Group Board level, and is a BSc Honours cell physiology graduate from Edinburgh University.

Kirsty qualified as a Chartered Accountant with KPMG London, and is a prize-winning Cell Physiology graduate from Edinburgh University,

Additional Members

Photo of Professor Steve Wilton

Professor Steve Wilton

Prof Wilton is director of the Center for Molecular Medicine and Innovative Therapeutics at Murdock University. He pioneered the development of the first FDA oligonucleotide therapy for Duchenne Muscular Dystrophy (eteplirsen).

Photo of Professor Merlin Thomas

Professor Merlin Thomas

Prof Thomas is Professor of Medicine at Monash University, Australia. He is currently developing inhaled oligonucleotide therapies for the lung in the context of Covid-19.

News & Events

Media Articles

Nature Outlook. October 2019.

It’s time for scientists to shout about RNA therapies.

Professor Lorna Harries Find Out More

INVITED REVIEW Frontiers in Genetics 2019.

RNA Biology Provides New Therapeutic Targets for Human Disease.

Professor Lorna Harries Find Out More

INTERVIEW: Longevity Technology. July 2020.

SENISCA seeks funding for senescence reversal.

Professor Lorna Harries Find Out More

Events

If you would like to meet us, SENISCA will be present at the following conferences and trade shows:

  • BioForward Conference: 5th October 2020 (Oxford, UK)

Members of the SENISCA team will be speaking at:

  • Advances in Cell and Tissue Culture Conference: Autumn (Cardiff, UK)
  • Science of Aging Virtual Symposium 2020: 16th September 2020 (Digitally)
  • Ending Age-related diseases 2020: 20th August 2020 (Digitally)
  • Fifth Eurosymposium on Healthy Ageing (EHA) 2021: Dates and venue TBA
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Photo of Fibroblast cells Senescent primary human fibroblast cells.
Image credit: Emad Manni, Harries Lab.

Publications

  1. Lee BP, Smith M, Buffenstein R & Harries LW. “Negligible senescence in naked mole rats may be a consequence of well-maintained splicing regulation.” GeroScience. 42(2), 633-651 (2020). doi:10.1007/s11357-019-00150-7
  2. Lye JJ*, Latorre E*, Lee BP, Bandinelli S, Holley JE, Gutowski NJ, Ferrucci L & Harries LW. “Astrocyte senescence may drive alterations in GFAPA, CDKN2A p14ARF and TAU3 transcript expression and contribute to cognitive decline.” GeroScience. 41(5), 561-573 (2019). doi: 10.1007/s11357-019-00100-3
  3. Latorre E, Ostler EL, Faragher RGA & Harries LW. “FOXO1 and ETV6 genes may represent novel regulators of splicing factor expression in cellular senescence.” FASEB J. 33(1), 1086-1097 (2019). doi: 10.1096/fj.201801154R
  4. Lee BP, Mulvey L, Barr G, Garratt J, Goodman E, Selman C & Harries LW. “Dietary restriction in ILSXISS mice is associated with widespread changes in splicing regulatory factor expression levels.” Exp Gerontol. 128, 110736 (2019). doi: 10.1016/j.exger.2019.110736
  5. Lee BP, Pilling LC, Bandinelli S, Ferrucci L, Melzer D & Harries LW. “The transcript expression levels of HNRNPM, HNRNPA0 and AKAP17A splicing factors may be predictively associated with ageing phenotypes in human peripheral blood.” Biogerontology. 20(5), 649-663 (2019). doi: 10.1007/s10522-019-09819-0
  6. Latorre E, Torregrossa R, Wood ME, Whiteman M & Harries LW. “Mitochondria-targeted hydrogen sulfide attenuates endothelial senescence by selective induction of splicing factors HNRNPD and SRSF2.” Aging (Albany NY). 10(7), 1666-1681 (2018). doi: 10.18632/aging.101500
  7. Latorre E, Birar VC, Sheerin AN, Jeynes JCC, Hooper A, Dawe HR, Melzer D, Cox LS, Faragher RGA, Ostler EL & Harries LW. “Small molecule modulation of splicing factor expression is associated with rescue from cellular senescence.” BMC Cell Biol. 18(1), 31 (2017). doi: 10.1186/s12860-017-0147-7
  8. Latorre E, Pilling LC, Lee BP, Bandinelli S, Melzer D, Ferrucci L & Harries LW. “The VEGFA156b isoform is dysregulated in senescent endothelial cells and may be associated with prevalent and incident coronary heart disease.” Clin Sci (Lond). 132(3), 313-325 (2018). doi: 10.1042/CS20171556
  9. Lee BP, Pilling LC, Emond F, Flurkey K, Harrison DE, Yuan R, Peters LL, Kuchel GA, Ferrucci L, Melzer D & Harries LW. “Changes in the expression of splicing factor transcripts and variations in alternative splicing are associated with lifespan in mice and humans.” Aging Cell. 15(5), 903-13 (2016). doi: 10.1111/acel.12499
  10. Holly AC, Melzer D, Pilling LC, Fellows AC, Tanaka T, Ferrucci L & Harries LW. “Changes in splicing factor expression are associated with advancing age in man.” Mech Ageing Dev. 134(9), 356-66 (2013). doi: 10.1016/j.mad.2013.05.006
  11. Harries LW, Hernandez D, Henley W, Wood A, Holly AC, Bradley-Smith RM, Yaghootkar H, Dutta A, Murray A, Frayling TM, Guralnik JM, Bandinelli S, Singleton A, Ferrucci L & Melzer D. “Human aging is characterized by focused changes in gene expression and deregulation of alternative splicing.” Aging Cell. 10(5), 868-78 (2011). doi: 10.1111/j.1474-9726.2011.00726.x

Contact

Senisca Ltd
RILD Building
Barrack Road
Exeter
EX2 5DW
T:+44 (0) 7515 454 146 Email Us
Photo of Endothelial cells Senescent primary human endothelial cells.
Image credit: Emad Manni, Harries Lab.