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

Research Team

Board Advisory

News & Events

Media Articles

Nature Biotechnology. November 2020

Send in the senolytics.

News Feature Find Out More

INTERVIEW: Longevity Technology. July 2020.

SENISCA seeks funding for senescence reversal.

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

Nature Outlook. October 2019.

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

Professor Lorna Harries Find Out More

Events

SENISCA will be attending the following conferences:

  • ICSA 2022: 29th September - 1st October 2022 (Groningen)
  • Mechanisms of Ageing: 27th September - 1st October 2022 (virtually)
  • BioSeed 2023: 23rd January 2023 (London)
  • 2nd annual mRNA Based Therapeutics Summit Europe: 24th - 26th January 2023 (Berlin)
  • Termis EU 2023: 27th - 30th March 2023 (Manchester)

Lorna Harries (CSO) will be speaking at:

  • Seminar for the Wellcome Wolfson Institute for experimental medicine: 7th November 2022
  • Brussels Eurosymposium on healthy ageing: 24th - 26th November 2022 (Brussels)
  • Annual South Coast RNA meeting: 16th December 2022 (Canterbury)
  • Proteomass splicing meeting 2023: 17th - 21st 2023 July 2023 (Lisbon)
Photo of Fibroblast cells Senescent primary human fibroblast cells.
Image credit: Emad Manni, Harries Lab.

Vacancies

Director of Oligonucleotide Chemistry and Delivery (Pre-Clinical Phase)

Location: Exeter or new satellite office (US, Europe or UK)
Start Date: Summer 2022 Working hours: This is a full or part time executive role

SENISCA is seeking a Director of Oligonucleotide Chemistry and Delivery to be in position by Summer 2022. This Executive level R&D position requires strategic thinking, an ability to work collaboratively with external CRO partners, portfolio mindset and deep scientific expertise across several of the following disciplines:

  • Oligonucleotide chemistry
  • Bioconjugation chemistry
  • Cellular and molecular pharmacology
  • Cell delivery technologies
  • Nanotechnologies
  • Understanding of the IP and regulatory landscape around oligonucleotide therapeutics.

This is an exceptional opportunity for the right candidate, joining SENISCA at the start of a high-growth journey for one of the UK's leading RNA medicine biotech spinouts.

This new Director-level position will join the existing cofounders' team of Chief Technical Officer, Chief Scientific Officer and launch Chief Executive Officer. It is intended that this role will be mainly based in Exeter UK, however there is potential for either a second UK-based SENISCA office, or a Europe or US-based satellite office or R&D base.

Core responsibilities include, but are not limited to:

  • A lead role in the execution of strategic plans to develop SENISCA's pipeline therapeutic programmes, from discovery through to lead candidate, cell delivery and clinical development
  • Supervise and manage third-party CRO collaboration and outsourced work as needed
  • Provide scientific direction, strategy and leadership for:
    • Novel oligonucleotide chemistry, discovery and formulation, in order to drive advancement of lead candidate selection and modification
    • Process development and optimization of oligonucleotide delivery for ex vivo testing phase, leading in time to in vivo testing phase, guided by a clear understanding of the regulatory landscape and IP requirements
  • Critically evaluate experiment data and communicate scientific findings as verbal presentations and written reports to relevant internal and external parties, including key SENISCA stakeholders and investors

Experience and skillsets to include all, or some of the below:

  • PhD degree in a synthetic organic, medicinal chemistry, or related scientific discipline. Postdoctoral experience with an emphasis on nucleic acid chemistry and/or nucleic acid cell delivery systems
  • A minimum of 5 years of experience in the biopharmaceutical industry with a proven track record of leading innovative oligonucleotide discovery and/or oligonucleotide delivery projects
  • Proven experience as a project leader in a biopharmaceutical or biotech industry
  • Strong track record of scientific contributions including peer reviewed first-author publications, patent applications, and/or presentations at major national meetings is preferred
  • Excellent interpersonal and presentation skills
  • A work ethic, sense of urgency, adaptability and enthusiasm that will allow the successful candidate to thrive in a fast-paced, cutting-edge research environment

Apply

Please send CV's and initial enquiries to hr@senisca.com addressed to Anna Bennett (SENISCA's business co-ordinator). We look forward greatly to hearing from you.

Publications

  1. Frankum R, Jameson TSO, Knight BA, Stephens FB, Wall BT, Donlon TA, Torigoe T, Willcox BJ, Willcox DC, Allsopp RC, Harries LW. "Extreme longevity variants at the FOXO3 locus may moderate FOXO3 isoform levels." Geroscience. (2021). doi: 10.1007/s11357-021-00431-0. Online ahead of print.PMID: 34436732
  2. Bramwell LR, Harries LW. Targeting Alternative Splicing for Reversal of Cellular Senescence in the Context of Aesthetic Aging. Plast Reconstr Surg. 147(1S-2):25S-32S. (2021) doi: 10.1097/PRS.0000000000007618.PMID: 33347071
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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
  12. 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
  13. 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.