Engineered Delivery for the Brain and Beyond

Our Research

Overview

Biomedicines hold immense promise for precision medicine, yet a fundamental challenge persists: ensuring that therapeutics are delivered with optimal specificity, localization, and control while minimizing systemic exposure and off-target effects. Our research programme seeks to address this challenge by leveraging cutting-edge protein engineering and synthetic biology to develop next-generation gene delivery technologies. A major focus of our work is the advancement of the SHielded, REtargeted ADenovirus (SHREAD) platform, a precision gene therapy system designed to transform target tissues into biofactories for therapeutic production, enabling highly localised drug expression with reduced systemic toxicity. This breakthrough approach has the potential to enhance the safety and efficacy of biologics across multiple therapeutic areas. Building upon this foundation, we aim to expand the application of SHREAD and related viral vector (VV) and virus-like particle (VLP) technologies to overcome delivery barriers in complex disease contexts, particularly within the central nervous system (CNS).

Research Background Illustration

Objective & Research Goals

Key objectives include developing neurotropic gene therapy vectors through capsid engineering and modular targeting adapters, optimising strategies for blood-brain barrier (BBB) delivery, and validating therapeutic efficacy in preclinical models of neurodegenerative diseases and neuro-oncology. By integrating expertise in protein engineering, synthetic biology, and molecular neuroscience, our research seeks to push the boundaries of precision gene therapy, positioning these technologies at the forefront of next-generation biologic therapeutics.

Mission & Vision

Mission: To enable next-generation cell and gene therapies by innovating delivery technologies, powered by protein engineering and synthetic biology, with a focus on overcoming delivery barriers in the central nervous system. 

Vision: To transform the treatment of complex diseases by establishing programmable, tissue-specific gene delivery as a core technology for precision medicine—starting with the brain and expanding beyond.

Selected Publications

Targeted adenovirus-mediated transduction of human T cells.
Mol Ther Methods Clin Dev, 2023

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CRISPR-clear imaging of melanin-rich B16-derived solid tumors.
Commun Biol, 2023

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NK cells with tissue-resident traits shape response to immunotherapy by inducing adaptive antitumor immunity.
Sci Trans Med, 2022

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The SHREAD gene therapy platform for paracrine delivery.
Proc Natl Acad Sci USA, 2021

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iMATCH: a modular system for high-capacity adenovirus gene therapy.
Mol Ther Methods Clin Dev, 2021

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Malignant tissues produce divergent antibody glycosylation.
MAbs, 2020

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Our Team

Sheena N. Smith, Ph.D.

Principal Investigator

Assistant Professor of Biotechnology

View NTU Faculty Profile

Dr. Sheena N. Smith is a newly appointed Assistant Professor of Biotechnology in the School of Chemistry, Chemical Engineering and Biotechnology (CCEB) at Nanyang Technological University (NTU), Singapore. She earned her Ph.D. in Biochemistry from the University of Illinois at Urbana-Champaign (USA) and completed postdoctoral training under Prof. Andreas Plückthun at the University of Zürich (Switzerland). She now leads a growing research programme at the interface of cell and gene therapy (CGT), protein engineering, and synthetic biology to overcome critical barriers in therapeutic delivery. She is a co-inventor of the SHREAD (SHielded, REtargeted ADenovirus) gene therapy platform for localised therapeutic delivery, and previously led its translational development at a Swiss biotech company. Now establishing her independent research programme at NTU, Dr. Smith is expanding her work into engineering new systems for targeted delivery to the brain, with applications in neurological diseases and neurooncology. Her goal is to enable more effective and safe use of next-generation therapeutic modalities, including genome editing machinery, complex immunotherapeutic combinations, and programmable gene circuits, by developing advanced delivery systems that bridge the gap between bench and bedside for emerging technologies.

Chanchal Sharma, Ph.D.

Postdoctoral Researcher & Lab Manager

Dr. Chanchal Sharma is a Postdoctoral Fellow at the Smith Lab, with research spanning neuroinflammation, mitochondrial dynamics, and gene therapy approaches for neurological disorders. In the Smith Lab, her research focuses on engineering humanized SHREAD viral systems for precise gene delivery, aimed at restoring blood–brain barrier integrity in Alzheimer’s disease.

Ankita Chowdhury, M.Tech

Ph.D. Student

Ankita Chowdhury is a Ph.D. student in the Smith Lab. She completed her M.Tech degree from the Indian Institute of Technology Delhi, India in Biomolecular and Bioprocess Engineering. Her previous work experience includes silica nanoparticle based targeted drug delivery in meningioma. Currently she is working on utilizing the SHREAD platform to deliver therapeutic payloads in glioblastoma.

Mujtaba Khan

Research Intern (MS-CSI)

Mujtaba Khan completed his Bachelor’s degree in Pharmacy from the University of Mumbai, India. His previous research experience includes the development of a dual Neprilysin–DPP inhibitor for the treatment of Type-II Diabetes, as well as investigating the impact of Corticosteroid-Binding Globulin (CBG) mutant variants on progesterone binding and their potential implications for pregnancy outcomes.

Kaashvie Jain

MSc Student (Project student)

Kaashvie Jain is a postgraduate biomedical engineering student undertaking her MSc research project in the Smith Lab. Her work focuses on cell culture techniques in neuroscience and contributes to ongoing research associated with the SHREAD gene therapy platform. The project forms part of her postgraduate training in experimental biomedical research.

Michael Tantoco

Final Year Project Student

Michael Tantoco is a Year 4 Chemistry and Biological Chemistry undergraduate student doing his Final Year Project in the Smith Lab. He is currently working with Ankita Chowdhury on developing the SHREAD platform for the treatment of glioblastoma.

News

SEACURE 2025

Smith Lab welcomes new student members at the start of the academic term

2026.01.12

The Smith Lab is pleased to welcome two new student members at the start of the academic term. Michael Tantoco has joined the group as a Final Year Project student in Chemistry and will be with the lab until May, while Kaashvie Jain has joined as a Master’s project intern and will remain with the group until June. We are delighted to welcome Michael and Kaashvie and look forward to their contributions over the coming months.

The Smith Lab marks the end of 2025 with its inaugural holiday gathering

2025.12.15

The Smith Lab celebrated the end of a productive year at Nanyang Technological University, Singapore with its inaugural holiday gathering. In true Singapore fashion, the evening included an escape room activity, dinner at a local hawker centre, and a visit to the Marina Bay Sands fountain and light show. The gathering brought together current team members as well as a soon-to-join member of the group. The lab is proud of the progress made in 2025 in establishing the laboratory and research programme, and looks forward to continued growth, collaboration, and discovery in 2026.

INNO APAC Tech Tour

Smith Lab awarded MOE Tier 1 research grant

2025.12.09

The Smith Lab has been awarded its first Tier 1 research grant from Singapore’s Ministry of Education (MOE). The funding will support the development of next-generation gene delivery technologies aimed at improving the safety, precision, and accessibility of systemic gene therapies. The project focuses on engineering new viral capsids designed to overcome pre-existing immunity, enabling redosing and providing a new scaffold for systemic gene therapy applications. The Smith Lab gratefully acknowledges the support of the Ministry of Education in enabling this research.

Singapore Scientific Conference 2025

2025.12.08-11

The Smith Lab participated in the Singapore Scientific Conference 2025 (SSC2025), held from 8-11 December at the Sands Expo and Convention Centre, Marina Bay Sands. The conference marked Singapore’s 60-year journey in science and technology and highlighted the nation’s sustained commitment to research, innovation, and future-focused scientific investment.

AGCTC flyer

Prof. Smith delivers invited talk on designing translation-ready gene therapy platforms

2025.12.03

Prof. Sheena Smith delivered an invited talk at the Cincinnati Children's Hospital Applied Gene and Cell Therapy Center (AGCTC) "Meet the Expert Series" on how gene therapy programmes can be designed from the outset to support scalability, manufacturability, and regulatory readiness. Drawing on experience from early-stage biotech discovery and CMC strategy, the lecture highlighted practical approaches for embedding CMC thinking early in academic research, reducing downstream manufacturing risk, and enabling smoother progression from preclinical development to GMP manufacturing and clinical translation.

SEACURE 2025

Smith Lab at Singapore International SEACURE+ Neurocognition Symposium 2025

2025.11.28

The Smith lab attended the launch of SEACURE+, a new NTU-led regional consortium bringing together clinicians and researchers across Southeast Asia to tackle dementia through coordinated neurocognition, neuroimaging, and biomarker research. This initiative marks an important step toward addressing region-specific aspects of brain health and reflects our lab’s interest in contributing to collaborative, translational efforts in neurological disease.

A*STAR Cell and Gene Therapy Flagship Seminar: SHREADing the Limits of Gene Therapy

2025.11.18

Prof. Sheena Smith delivered a talk titled “SHREADing the Limits of Gene Therapy: Precision Delivery for Oncology and Beyond” at the A*STAR Cell and Gene Therapy (CGT) Flagship Seminar Series, highlighting the SHREAD gene therapy platform and its engineering principles for precise, tissue specific delivery of large genetic payloads in vivo, with applications ranging from solid tumours to emerging work in central nervous system targeting. The seminar also featured A/Prof Eddie Tan (CoRE, Duke-NUS), who provided an overview of Singapore’s regulatory landscape for cell, tissue, and gene therapy products, placing the scientific advances in a translational and regulatory context.

Prof. Smith on an immersive tour of China’s biotechnology and innovation landscape

2025.11.02-08

Prof. Sheena Smith was invited to participate in the INNO-APAC China Biotech Tour alongside a distinguished group of academic leaders, company founders, and industry executives on a one-week programme spanning Shanghai, Shaoxing, and Shenzhen, offering an immersive introduction to China’s rapidly evolving biotechnology and technology ecosystem; during the Shanghai leg, she delivered an invited talk entitled "Engineering the Future of Cell and Gene Therapy (CGT): Precision Delivery Innovations Across the US, Europe, and Asia-Pacific" at the Shanghai Global Talents Pudong Biomedicine Session, highlighting translational perspectives and emerging delivery strategies shaping the global CGT landscape.

SRIS Appointment

Prof. Smith Appointed as SRIS affiliate member

2025.10.17

Prof. Sheena Smith has been appointed as an Affiliate Member of the Skin Research Institute of Singapore (SRIS), a tripartite research institute jointly established by A*STAR, the National Healthcare Group (NHG), and Nanyang Technological University (NTU). This appointment recognises Prof. Smith’s contributions to translational biomedical research and supports her engagement in multidisciplinary collaborations within SRIS, including participation in joint research projects, access to shared research resources, and involvement in SRIS scientific programmes and activities.

Smith lab visits ACTRIS to explore Singapore’s Cell and Gene Therapy manufacturing ecosystem

2025.10.17

Members of the Smith Lab visited the Advanced Cell Therapy and Research Institute, Singapore (ACTRIS) for a meeting with institute leadership and a facility tour to learn more about Singapore’s rapidly advancing cell therapy manufacturing capabilities. The visit highlighted ACTRIS’s purpose-built, scalable infrastructure for early-stage development and clinical translation, underscoring the strong momentum building within Singapore’s cell and gene therapy ecosystem.

Prof. Smith Attends ESGCT Annual Congress in Seville as NTU CCEB Delegate

2025.10.07-11

Prof. Sheena Smith attended the Annual Congress of the European Society of Gene and Cell Therapy (ESGCT) in Seville, Spain, as an official delegate of the School of Chemistry, Chemical Engineering and Biotechnology (CCEB) at Nanyang Technological University. The ESGCT meeting brought together leading researchers, clinicians, and industry partners from across Europe and beyond to discuss the latest advances in gene and cell therapy, spanning vector engineering, manufacturing, clinical translation, and regulatory science. During the congress, Prof. Smith enjoyed reconnecting with long-standing collaborators and engaging with colleagues from both academia and industry, and looks forward to strengthening and expanding ongoing collaborations with European partners in the years ahead.

Prof. Smith delivers keynote at the BPD Biopharmaceutical Bioprocess Development Summit Singapore

2025.09.24-26

Prof. Sheena Smith was invited as a Keynote Speaker at the BPD | Biopharmaceutical Bioprocess Development Summit, held at Marina Bay Sands, Singapore, where she delivered a keynote entitled "From Academia to Biotech: Building Gene Therapy Platforms Toward Clinical Translation." Her talk examined why many cell and gene therapy programmes encounter bottlenecks at the manufacturing stage, despite strong preclinical efficacy, and outlined practical strategies for designing gene therapy platforms with scalability, manufacturability, and regulatory readiness in mind from the outset. Drawing on experience leading and advising early-stage discovery and CMC programmes in biotech, Prof. Smith discussed engineering for reduced complexity, embedding CMC thinking early in academic research pipelines, and positioning CDMOs as strategic partners to support efficient tech transfer and clinical execution. As part of the summit, Prof. Smith was also invited to tour the new WuXi XDC Singapore site currently under construction, a large-scale facility designed to support 2,000 L batches and up to eight million vials of bioconjugates annually, further highlighting Singapore’s growing role as a global hub for advanced biopharmaceutical manufacturing

NNI Talk

Prof. Smith Delivers Invited Seminar at the National Neuroscience Institute, Singapore

2025.09.08

Prof. Sheena Smith delivered an invited seminar at the National Neuroscience Institute (NNI), Singapore, titled The SHREAD Gene Therapy Platform: Engineering Precision Delivery for Cancer, Neurological Disease, and Beyond. The talk outlined the design and translational potential of the SHREAD platform for cell- and tissue-specific delivery of large genetic payloads, with highlights spanning targeted cancer therapies and emerging applications in neurological diseases, including glioblastoma and Alzheimer’s disease.

LKC Medicine Talk

Prof. Smith Delivers Invited Seminar at LKCMedicine, Novena

2025.08.29

Prof. Sheena Smith gave an invited seminar at the Lee Kong Chian School of Medicine Novena campus on the development of the SHREAD gene therapy platform and its application to precision delivery of complex genetic payloads in vivo. The presentation traced the evolution of SHREAD from oncology-focused programmes to emerging efforts in neurological disease, highlighting strategies for localised therapeutic expression, blood-brain barrier targeting, and spatial control within the central nervous system, and stimulating discussion around future cross-disciplinary collaborations.

Smith Lab welcomes first members and holds inaugural group meeting and lunch

August 2025

The Smith Lab marked an exciting milestone with its first group meeting on 22 August, followed by a welcome lunch on 1 September to celebrate the growth of the team. These early gatherings brought the lab together to set shared goals and build momentum, while welcoming its first members: Chanchal Sharma, Postdoctoral Researcher who joined on 18 August from the Byrd Alzheimer’s Center of the University of South Florida, bringing extensive expertise in neurodegeneration and in vivo disease models, and Ankita Chowdhury, Ph.D. student who joined on 8 August from the Indian Institute of Technology Delhi, with a strong background in biomolecular engineering, nanomedicine, and translational cancer research. Together, these events marked the formal start of Smith Lab operations at Nanyang Technological University.

Prof. Smith attends and delivers invited talk at the SCGT Pan Asia Summit 2025

2025.07.16-18

Prof. Sheena Smith participated in the Singapore Cell and Gene Therapy (SCGT) Pan Asia Summit 2025, held at Biopolis from 16–18 July 2025, and delivered an invited talk entitled "Turning Tumours into Biofactories: The SHREAD Gene Therapy Platform for Localised Therapeutic Delivery. The presentation highlighted the engineering of the SHREAD platform for cell- and tissue-specific delivery of large or complex genetic payloads, with published studies demonstrating localised, in situ production of therapeutic antibodies within the tumour microenvironment to achieve sustained expression and reduced systemic exposure. Prof. Smith also outlined how these principles are being extended to neurological disease, underscoring SHREAD’s potential as a versatile platform for precision gene therapy across challenging disease contexts.

Prof. Smith Attends the 16th International Adenovirus Meeting (IAMXVI) in Cardiff, Wales

2025.07.07-11

Prof. Sheena Smith attended the 16th International Adenovirus Meeting (IAMXVI) in Cardiff, Wales, a biennial conference that brings together international experts working across adenovirus biology, vector engineering, and translational applications. The meeting provided a valuable forum for in-depth scientific exchange spanning fundamental virology, vector design, manufacturing, and clinical translation. Prof. Smith enjoyed reconnecting with long-standing colleagues within the adenovirus community, sharing updates on her newly established lab at Nanyang Technological University, and engaging in discussions that will inform future collaborations at the interface of adenovirus engineering and next-generation gene therapy.

Smith Joins NTU

Prof. Smith begins appointment as Assistant Professor of Biotechnology at NTU

2025.05.19

Prof. Sheena Smith marked her first day at Nanyang Technological University as an Assistant Professor of Biotechnology, formally launching her independent research programme. Her work sits at the intersection of protein engineering, vector engineering, and synthetic biology, with a focus on advancing the SHREAD gene therapy platform and developing next-generation delivery systems for the central nervous system.

Openings

We welcome interest from motivated researchers and students across all levels. Please explore current opportunities below:

Contact Us

School of Chemistry, Chemical Engineering and Biotechnology (CCEB)
Nanyang Technological University
70 Nanyang Drive
Singapore 639798
NTU Logo Research Laboratories: N1.3 B3-15, B3-23, & B4-18

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