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

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

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

  • AMWC 19th aesthetic and anti-aging medicine world congress: 16th - 19th September 2021
  • 3rd Meridian drug discovery meeting: 18th - 19th November 2021
  • Longevity Leaders World Congress 2022: 26th - 27th April 2022
  • Advanced Therapies Congress 2022: London, 23rd – 25th May 2022

Members of the SENISCA team will be speaking at:

  • Allergan Science of Aging (SoA) symposium: Beijing, 15th September 2021 (Digitally)
  • Fifth Euro symposium on health ageing: 1st October (Digitally)
  • British Geriatrics Society: 25th November 2021
  • MIAM 2021: 10th Chinese Annual Meeting of Minimally Invasive Aesthetic Medicine (MIAM): 17th December 2021
Photo of Fibroblast cells Senescent primary human fibroblast cells.
Image credit: Emad Manni, Harries Lab.

Vacancies

Scale-up Chief Executive Officer

Location: Exeter or new satellite office (US, Europe or UK)
Start Date:Summer 2022

SENISCA is seeking a scale-up CEO to be in position by Summer 2022. This Executive level position will drive innovation, scientific excellence and commercial success, leveraging their significant expertise to develop therapeutic solutions from discovery stage through to clinical development. This exceptional opportunity is a leadership role, at the start of a high-growth journey for one of the UK’s leading RNA medicine biotech spinouts.

This will be SENISCA’s first executive team expansion. The aim of which is to ensure the right breadth of skillsets and experience within the executive team, with sufficient lead time ahead of a Series A fundraise (late 2023) and clinical development phase (from 2024). This new scale-up CEO position will join the existing co-founders team of Chief Technical Officer, Chief Scientific Officer and launch Chief Executive Officer (the current founders role of launch CEO is anticipated to move across to Chief Operations Officer during late 2022).

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:

  • Oversee the execution of strategic plans to develop and commercialise SENISCA’s pipeline therapeutic programmes, from discovery through to lead candidate and clinical development.
  • Develop relationships with external partners (including CRO’s and Pharmaceutical co-development partners) to leverage resources to advance pipeline, secure co-development partnerships and progress global in/out licensing deals.

Experience and skillsets to include:

  • Expertise (scientifically or commercially) in an area of RNA therapeutics, or within any of the broad range of age-related disease(s) targeted by SENISCA’s platform technology.
  • Track record of achievement in driving biotech programmes or initiatives to milestones.
  • Fundraising experience, at any stage from discovery through to clinical phase or IPO.
  • IP strategy setting experience and/or pharmaceutical sector global licensing experience.
  • A willingness to carry out broad and diverse workflow responsibilities to support high growth and rapid team expansion.
  • 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.
  • Excellent interpersonal and presentation skills.
  • Strong influencing and negotiating skills.

Please send CV’s and initial enquiries to hr@senisca.com addressed to Anna Bennett (SENISCA’s business co-ordinator), within the initial application window of the 1st to 31st of October 2021. We look forward greatly to hearing from you.

Apply

Scientific Advisory Board Expansion

Location: Exeter or on-line meetings.
Start Date:Spring 2022

SENISCA is seeking to expand its Scientific Advisory Board [SAB] with 3 new members. SAB members will be expected to attend quarterly meetings to support SENISCA’s Chief Scientific Officer and Executive team across each R&D division of the business. Meetings will be either in-person at SENISCA’s Exeter UK-based R&D lab facilities or on-line via Zoom.

We are looking for either academic, biotech or pharmaceutical sector individuals with the following experience. Our aim is that at least 2 of the 3 candidates will have an oligonucleotide drug development background:

  • A track record of accomplishments in leading drug discovery teams from target identification through delivery of clinical candidates and establishing clinical translational strategy.
  • Expertise (scientifically or commercially) in an area of RNA therapeutics, ideally oligonucleotides, or within any of the broad range of age-related disease(s) targeted by SENISCA’s platform technology.
  • Expertise in oligonucleotide synthesis and chemical modification.
  • Expertise in oligonucleotide cell delivery technology.

Please send CV’s and initial enquiries to hr@senisca.com addressed to Anna Bennett (SENISCA’s business co-ordinator), within the initial application window of the 1st to 31st of October 2021. We look forward greatly to hearing from you.

Apply

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.