Harnessing Regenerative Gene Therapy for the Treatment of Cystic Fibrosis Lung Disease

About the Project

Cystic fibrosis (CF) is a chronic airways disease caused by mutations in a cAMP-dependent chloride channel called the cystic fibrosis transmembrane conductance regulator (CFTR). In the lungs, defective ion channel activity and mucus obstruction results in chronic cycles of infection and inflammation, with tissue damage leading to progressive lung function decline and premature death. Treatment is complicated by the presence of >2000 disease-causing mutations that reduce either the quality of quantity of CFTR protein. CFTR modulators, including the triple combination Kaftrio (ETI; Elexacaftor Tezacaftor Ivacaftor; Vertex Pharmaceuticals), have significantly improved outcomes. However, these mutation-specific treatments are ineffective or unsuitable for some individuals, with disproportionate impact on those from ethnic minority backgrounds, who often carry unresponsive genetic variants. ETI therapy also presents significant economic and clinical challenges that severely restrict global accessibility; currently, only 12% of pwCF worldwide receive modulators. Concerns around variable clinical responses, tolerability and incomplete restoration of CFTR function (only 50% of normal) also highlights the urgent need for alternative or synergistic treatments.

Gene therapy technologies for delivering nucleic acid-based therapeutics promise extraordinary potential for previously untreatable indications. Current delivery technologies using nanoparticles and viral vectors have issues around safety and lack selective and efficient delivery to tissues. Pipeline CF gene therapies also fail to address the issue of existing lung damage and loss of pulmonary function due to chronic inflammation, scarring and fibrotic lung tissue remodelling. A regenerative approach to restore lost lung function is therefore required to further impact survival.

OmniSpirant is a biotechnology SME whose OmniSome technology offers an innovative inhaled regenerative gene therapy technology for treating serious CF. The technology is based on biological (non-viral) nanoparticles, called extracellular vesicles (EVs), produced from stem cells (MSC) and engineered to transport and deliver the normal CFTR gene. Surface engineering of disease targeting gene therapy EVs also facilitates mucus penetration and intracellular uptake. In initial validation studies (Martin Lab, QUB funded by an Emily’s Entourage Award (2023-2025), EVs were shown to restore CFTR ion channel activity to CF cells in 3D airway cell culture models. MSC EVs have also widely demonstrated regenerative potential via stimulation of repair mechanisms as well as beneficial immuno-modulatory and anti-inflammatory effects via a variety of factors (e.g., microRNAs, mRNAs).

The objectives of this current PhD opportunity are:

• To work with OmniSpirant to further engineer MSC-EVs to enhance CFTR activity and ensure cell-specific CFTR expression in target cells.
• To assess the CFTR-corrected response in bronchial epithelial cells as well as the anti-inflammatory effect of various populations of bio-engineered EVs in the presence of pro-inflammatory stimuli.
• To investigate any potential rescue of anti-fibrotic effects via suppression of TGF-beta signalling in lung fibroblasts and small airway epithelial cells.

These studies directly align to the strategic research interests of the Martin group and builds on a collaborative relationship with OmniSpirant which was initially supported by the €8.9M BREATH (Border REgions Airways Training Hub). The development of a potentially ground-breaking respiratory EV therapeutic programme fits with the School, Faculty and institutional strategies in terms of reputation-building through the delivery of high quality, impact-driven, translational research.

Briefly describe the training that will be provided through the research project

The student will benefit from a unique collaborative training environment that combines academic excellence with industry-led translational expertise. They will join a multidisciplinary team focused on translational respiratory health research, gaining direct experience in collaborative, goal-oriented projects at the interface of basic science and therapeutic development.

The industry-supported funding package will provide access to advanced training and specialist methodologies. The student will receive hands-on training in a broad range of laboratory techniques, including cell and molecular biology, protein characterisation, imaging approaches, and the differentiation of primary human airway epithelial cells at the air-liquid interface, together with other functional ex vivo models. In addition, formal secondments with OmniSpirant Therapeutics will provide exposure to cutting-edge bioengineering and other biotechnological approaches. Training will include extracellular vesicle (EV) surface engineering, genetic modification, and scale-up production technologies, enabling the student to develop a strong understanding of the translational pipeline from discovery science to therapeutic manufacture. This will ensure acquisition of skills that are highly relevant to both academic and industry career pathways.

Briefly outline the expected impact activities

Joint supervision and mentoring by the Martin and Taggart groups (QUB) working in collaboration with OmniSpirant R&D staff scientists will provide a structured training and management programme. This will maximise integration across both environments, supporting research independence, career planning, and professional development. Access to company facilities, equipment, and in-kind contributions will allow the generation of a substantial body of data to underpin both the doctoral thesis and publications in high-impact journals. This environment will provide a unique opportunity for the student to develop as both an independent researcher and team scientist

A dedicated travel and training budget will also enable presentation of research findings at international conferences, fostering communication skills and professional networking. Participation in industry-led events, conferences, research team and outreach activities will further develop transferable skills in leadership, teaching and public engagement.

Further funding details

To be eligible for consideration for a DfE Studentship a candidate must satisfy all the eligibility criteria based on nationality, residency, and academic qualifications. The Studentship is open to UK and ROI nationals, and to EU nationals with settled status in the UK, subject to meeting the specific DfE nationality and residency criteria. Full eligibility information can be viewed at: https://www.nidirect.gov.uk/articles/department-economy-postgraduate-studentship-scheme

Funding Notes

CAST (Co-operative Awards in Science and Technology) Collaborative PhD Studentship funded by the Department for the Economy, supported by OmniSpirant Therapeutics Ltd.

A CAST award provides for the payments of approved QUB tuition fees and the maintenance of students on Research Studentships (2024-25 stipend rate was £19,237 per annum; 2025-26 rates to be announced) intended to encourage the development of collaboration between universities and industry and, in particular, to provide an opportunity for graduates to start PhD research of direct interest to industry. The studentships will have the normal conditions for DfE awards. DfE studentships are for 3 years.

References

"Cystic Fibrosis
Gene Therapy
Extracellular Vesicles (EVs)
Regenerative Medicine
Nanoparticles
Inflammation"