Deliverics; Non-viral, non-toxic DNA delivery agents for cells and tissues
Submitting InstitutionsUniversity of St Andrews,
University of Edinburgh
Unit of AssessmentChemistry
Summary Impact TypeTechnological
Research Subject Area(s)
Technology: Medical Biotechnology
Medical and Health Sciences: Pharmacology and Pharmaceutical Sciences
Summary of the impact
Impact: Economic. The EaStCHEM spin-out company
Deliverics has commercialised biodegradable transfection reagents for both
the "research tool" and the "RNAi therapeutics" markets (globally valued
at £400M and £4 billion respectively). Beneficiaries are the
pharmaceutical and biotechnology sectors, and clinicians. The turnover
since 2010/11 is £330k and the company currently has five employees.
Significance: Deliveric's agents out-perfom existing materials in
term of efficacy and reduced levels of toxicity. They are not hampered by
the immunogenicity, manufacturing issues, and carcinogenicity previously
seen for viral vectors used as delivery agents. This presents a wide
ranging ability to deliver nucleic acids into cells and tissues for
Research; date; attribution: EaStCHEM research (2008) led by
Bradley reported a family of non-viral DNA delivery agents that offered a
highly-efficient and non-toxic method of delivering siRNA/DNA into
mammalian cells and tissues. Development and patenting of this technology
led to the spin-out of Deliverics Ltd. in 2010.
Reach: International customer base (20 research groups and 10
companies) including specially appointed distributors in Spain (Albyn
Medical), South Korea (CoreSciences), and US (Galen).
Background: The delivery of nucleic acids into cells is a
requisite for numerous biological / biomedical applications, ranging from
therapeutic (e.g. corrective gene therapy, gene silencing therapy, etc.)
to routine in vitro cell-based assays. Due to the founding role of
DNA and RNA molecules in all cellular processes, their transport into
cells is restricted by the cell membrane. Many different physical,
chemical and biological approaches have been explored for the cell
delivery of nucleic acids, with viral vectors being the most efficient one
both therapeutically or as a research-enabling tool. However, due to the
limitations of viral agents (antigenicity, risk of mutagenesis, production
costs, etc.), chemical delivery systems represent an attractive
alternative but have serious toxicity issues. Most chemical transfection
technologies are based on the use of large surfactants / polycationic
molecules with the ability to complex nucleic acids into liposome-like
particles and carry them into cells via endocytosis.
Research Following their move to EaStCHEM in 2005, the Bradley
group attracted significant support from the MRC and EPSRC (2005-2008
& 2009-2012) as well as from Scottish Enterprise (2008-2010), to
develop non-toxic cationic lipids and dendrimers as DNA/RNA carriers .
In early development work, two families of transfection reagents, based on
the rational assembly of naturally-occurring components such as amino
acids, lipids and non-toxic linkers stood out.[2,3]
This novel non-viral chemical approach offered a highly-efficient and non-toxic
a. Deliver nucleic acids (siRNA/DNA) to a wide range of
mammalian cell lines and tissues that cannot be transfected without
toxicity by existing commercial non-viral materials such as embryonic stem
b. Deliver gene therapy drugs with high efficiency, e.g. for the
delivery of RNAi-based therapeutics, an emerging application within the
Bio-Pharmaceutical sector. Gene therapy drugs have not yet been approved
in Europe or USA because of lack of safety and efficiency; however the
in-built degradation propensity of these reagents confers upon them the
ability to metabolize into natural products and enhance nucleic acid
release within the cell thus improving the delivery process.
For the latter, preliminary in vivo assays demonstrated the
ability of compounds to transfect mouse lung with no obvious signs of
toxicity, attracting early interest from major market players such as
Merck and Silence Therapeutics Plc. Therapeutic relevance for this is for
genetic diseases such as cystic fibrosis (annual treatment cost per
patient up to £160,000, 9000 sufferers in the UK, 40,000 in the US) and
viral infections such as influenza (annual cost to the US economy up to
£110bn, based on average 200,000 hospitalisations and 41,000 deaths).
The new series of biodegradable delivery reagents were patented in 2007
 and the spin-out company Deliverics Ltd created in 2010 for
their commercialization. Preliminary in vivo assays demonstrated
their ability to transfect DNA plasmids into mouse lung . Improved in
vivo biodegradable reagents were then developed in the Bradley group
[3,4] and patented in 2010. Their subsequent research and development
led to water-based formulations (SAFEctinTM product series)
that allow a one-step `mix & go' procedure. Ongoing research shows
outstanding transfection performance including with difficult-to-transfect
and sensitive cells. Additional in vivo assays have demonstrated
their ability to transfect siRNA and miRNA in mouse lung and skin
xerographs (unpublished data by Deliverics) with no signs of toxicity.
The unique selling points that distinguish the reagents from existing
platforms, and have allowed the research commercialisation are:
- High efficiency transfection (comparable/better than gold-standard
commercial products, Lipofectamine2000 and Effectene) in a variety of
mammalian cells, including stem cells.
- Ease of use (no requirement for later removal, enabling a simple,
- Cationic lipids specifically designed to be metabolised in vivo
rendering them non-toxic and safe for clinical applications (e.g.
- The combination of reduced toxicity and increased transfection
efficiency makes the compounds particularly amenable for in-vivo
Additionally, they do not incur the expensive and difficult 'Good
Manufacturing Process' requirements of viral production.
Key people who led the research
Professor Mark Bradley 2005 to date (EaStCHEM); Dr A. Unciti-Broceta 2005 - 2010 (EaStCHEM).
Research team members: A. Liberska, A. Lilienkampf, L. Moggio, L.
Pidgeon, A.R. Turner (EaStCHEM PhD and PDRAs) E. Holder, L.J. Jones, B.
Stevenson, D.J. Porteous, A.C. Boyd, K. Dhaliwal & C. Haslett (College
of Medicine and Veterinary Medicine, UoE). Our embedded business
development executive Dr Keith Finlayson was involved throughout the
process from application to now and continues to liaise with the company
in managing the patent portfolio for both parties ensuring a productive
relationship is maintained.
References to the research
A. Key papers: Underpinning research has been published in
international, high-quality, peer reviewed, academic journals and
receives citations from across the research area:
 *Tripod-like cationic lipids as novel gene carriers; A.
Unciti-Broceta, E. Holder, L.J. Jones, B. Stevenson, A.R. Turner, D.J.
Porteous, A.C. Boyd, M. Bradley, J Med Chem. 2008, 51,
15 cits, JIF 5.6.
 *Safe and efficient in vitro and in vivo
gene delivery: Tripodal Cationic Lipids with Programmed Biodegradability,
A. Unciti-Broceta, L. Moggio, K. Dhaliwal, L. Pidgeon, K. Finlayson, C.
Haslett, M. Bradley, J. Mat. Chem, 2011, 2154-2158.
doi:10.1039/C0JM03241G. 5 cits, JIF 6.1.
 *Solid-Phase Synthesis of Arginine-Based Double-Tailed Cationic
Lipopeptides: Potent Nucleic Acid Carriers. A. Liberska, A. Lilienkampf,
A. Unciti-Broceta, M. Bradley. Chem. Comm. 2011, 47,
4 cits, JIF 6.4.
 A. Unciti-Broceta, J. J. Díaz Mochón, R. M. Sanchez-Martin & M.
Bradley. The Use of Solid Supports to Generate Nucleic Acid Carrier, Acc.
Chem. Res. 2012, 45, 1140-1152. doi:10.1021/ar200263c.
5 cits, JIF 20.8.
B. Key patents:
 Cationic Lipids, Inventors: Unciti-Broceta A.; Bradley M.. Priority
Date: 19/10/2007. Published as WO2009050483.
 Cationic Lipids: second generation compounds, Inventors:
Unciti-Broceta A.; Liberska A.; Bradley M.. Priority date: 18/05/2010.
Published as WO2011144892.
C. Key Grants:
(i) Bradley, MRC/EPSRC G0401194 `High Throughput Chemical Biology —
Transfection Microarrays and Combinatorial Chemistry' £263,990 (2005).
(ii) Unciti-Broceta & Bradley, Scottish Enterprise proof-of-concept
award (10-CHM-001) `Non-Toxic DNA Delivery' £248,187 (2008).
(iii) Bradley, MRC G0801908, Multiplexed in vivo optimisation of
non-toxic gene transfer agents' £646,272 (2009).
(iv) Venture funding £205K (2010).
Details of the impact
The new chemical reagents for transfection described and protected
(above) were licenced to Deliverics, a new company which specialises in
cellular delivery products and technologies, spun out of EaStCHEM in
November 2010. Deliverics used the IP in both the in vitro reagent
market as well as having longer-term interests in in vivo uses.
These unique, chemical-based, biodegradable transfection reagents have
broken into both the "research tool" (reagent) and the "RNAi therapeutics"
(drug delivery) markets, delivering economic, human capital, and potential
A. Economic: spin-out of the company Deliverics
The significance of Deliverics' commercialised biodegradable
transfection reagents impacts on both the "research tool" and the "RNAi
therapeutics" markets and arises from their ability to out-perform
existing materials, without the immunogenicity, manufacturing issues, and
carcinogenicity previously seen for current viral vectors used as delivery
agents. This presents a wide ranging ability to deliver nucleic acids into
cells and tissues for biological applications.[S1]
The reach of the company is international, despite its youth. It
has an international customer base, including specially appointed
distributors in Spain (Albyn Medical), S. Korea (CoreSciences), and US
(Galen).The customer base (20 research groups and 10 companies) spans 5
countries. at Scottish Enterprise Enterpreneurial Support Manager has
said, "There is significant scope for Deliverics to expand its
distribution network overseas. We're very positive about the future and
looking forward to working with them as they continue to grow."[S2]
The turnover of the new company is £330k to date.[F1]
Deliverics Ltd has so far launched the following products:[F1]
- SAFEctinTM is a biodegradable transfection kit.
- SAFEctinTM-STEM is targeted at the stem cell market, a
market estimated at £100M pa. This reagent offers over 90% transfection
efficiency of RNA into stem cells in a simple, one-step protocol.
- New SAFEctin beta product, developed with TSB grant — out performing
SAFEctin, SAFEctin STEM, HappyFect and LipoFectamine 2000 in siRNA
delivery, and showing >70% transfection efficacy in notoriously
difficult cell types such as human fibrosarcoma HL116, primary mouse
lobular breast cancer cells, mouse embryonic limb cells and primary human
'[Text removed for publication].' [S3]
'The product that Deliverics has developed is a simple one-step
protocol that is easy to perform and produces very high transfection
efficiencies of our embryonic stem cells. During use, cells exhibited
high levels of expression and remained healthy. I think this is a great
product that will become market-leader over time.'[F2]
B. Human Capital:
Deliverics employs 5 people (4 PhD level).
C. Impact Development Timeline:
2008 Unciti-Broceta and Bradley awarded "Proof of Concept" grant (£250K)
from Scottish Enterprise to develop patent  into a commercial product.
4/2010 Deliverics Ltd spun-out. Registered in Companies House, #SC377672.
11/2010 (1) University of Edinburgh licenses patents  and  to
(2) Venture funding of £275K raised [S4]. Company valuation of £705K.
(3) First product, SAFEctin Transfection Reagent, launched.
(4) Dr Asier Unciti-Broceta awarded Nexxus `Young Life Scientist of the
2011 (1) Second core product, SAFEctin STEM launched.[S5]
(2) Internationalisation begins: Albyn Medical S.A. appointed as
distributor of Deliverics products in Spain. CoreSciences appointed as
distributor of Deliverics products in South Korea. Distribution deal in
the US with Galen Laboratory Supplies, giving access to the £130m US
transfection reagent market, a market with 8 % annual growth.[S6]
(3) Deliverics wins `Nexxus Most Promising Young Life Science Company of
(4) SE SMART: SCOTLAND Feasibility Study awarded for RNA transfection and
new transfection product for stem cells (SMART ref 10-9174; £63K; 2011).
(5) TSB Feasibility Study awarded to develop new protein delivery
technology (TSB ref 130436 and 130436; £50K; 2011 & 2012).
2012 (1) TSB Smart PoC grant awarded (to develop in vivo
transfection reagent prototype) (TSB ref 710195; £60K; 2012).
(2) TSB Collaborative R&D Grant awarded (TSB ref 101229; £94K; 2012);
TSB Collaborative R&D Grant awarded to joint consortium of AvantiCell,
Deliverics, and Synpromics (£263K, 2012).[S8]
(3)Deliverics CSO Dr Unciti-Broceta receives Royal Society of Chemistry
Young Industrialist of the Year Award.
Sources to corroborate the impact
[F1] Testimony from Deliverics' CSO confirming corroboration of turnover
and product range.
[F2] Testimony from Head of Production and Quality Control at R
Biomedical (Deliverics customer)
[S1] Deliverics' website http://www.deliverics.com/home/index.php/aboutus.
[S2] Scottish Enterprise press release on Deliverics (quote from their
Entrepreneurial Support Manager, High Growth Start-up unit on company's
rate of growth).
[S3] [Text removed for publication] Deliverics customer showing efficacy
of Deliverics products (results from pages 13 onwards).
[S4] The Scotsman: `New spin-out wins early stage funding' (website
[S5] Deliverics' Press release on Safectin STEM launch, Aug 2011.
[S6] Deliverics' $200M USA distribution deal, Oct 2011 (Lifescience
[S7] Press release on Deliverics' 2011 Nexxus Award (Scottish Life
Science Business award).
[S8] Synpromics website announcing collaborative TSB award with
Deliverics and Avanti (tiny url