About

Dr. Derfogail Delcassian is a distinguished researcher specializing in immunoengineering and biomaterials with a focus on developing innovative strategies for cell transplantation and immune modulation. Her work includes designing immune-isolation microcapsules with magnetic retrieval and imaging capabilities to protect beta cells for diabetes treatment, as well as creating lipid nanoparticle-based cancer vaccines that stimulate immune cells through the STING pathway. Dr. Delcassian's research also explores biomaterials to direct regulatory T cell behavior and immunoprotective strategies for islet transplants, aiming to enhance localized immune tolerance and improve transplant outcomes. Throughout her career, Dr. Delcassian has been recognized with numerous prestigious awards and fellowships, including the Marie Curie Sklodowska Fellowship for her work on immunoprotective beta cell transplants, the IUPAC 100 Younger Chemists award, and the EPSRC E-TERM Fellowship focused on biomaterial drug delivery depots for immune cell recruitment. She has contributed to advancing nanomedicine and tissue engineering by developing biofabricated nanoscale tools to investigate cellular behavior and immunomodulatory biomaterials for wound healing. Dr. Delcassian has also engaged in entrepreneurship and policy outreach, participating in programs such as the MIT Impact Fellowship and the MIT/Harvard/Sloan Biomedical Entrepreneurship program to translate her research into impactful applications. Dr. Delcassian's academic journey includes doctoral research at Imperial College London, where she was awarded the Imperial Doctoral Prize and worked on biomimetic interfaces and nanopattern systems to communicate with T cells. She has presented her research at prominent conferences and institutions, including the NIH Protein and Biotechnology Research Day and the Koch Institute at MIT. Her interdisciplinary approach combines materials science, immunology, and engineering to develop convergent strategies for cancer therapies and regenerative medicine, positioning her as a leading figure in the field of nanomedicine and immunoengineering.

Research topics

• Nanotechnology
• Materials science
• Chemistry
• Biology
• Radiology
• Biochemistry
• Cell biology
• Surgery
• Biomedical engineering
• Medicine

Selected publications

• Tunable Enhancement of T Cell Expansion Through Modulation of Stiffness and Adhesion Receptor Engagement in an Engineered Hydrogel Platform

  Advanced Materials · 2026-01-08

  articleOpen accessSenior author

  Adoptive T cell therapies (ACT) are an important class of oncology treatments that require ex vivo T cell expansion for clinical success. Technologies that can control both phenotype and yield in expanded cell products are highly desired. Here, we develop a new hydrogel scaffold for controlled T cell expansion with yields of up to 2000× fold in two weeks, compared to other hydrogel constructs (≈250×) and Dynabeads (≈1200×). Our 2D polyethylene glycol diacrylate (PEGDA) hydrogel scaffold is cross-linked with streptavidin moieties to present various biotinylated ligands to cells with controlled hydrogel stiffness (PEGDA-Strep). Using this platform, we demonstrate that combining substrate stiffness with adhesion receptor ligands (aLFA-1 or aCD2) dictates T cell activation and proliferation. On stiff substrates, these ligands drove expansions 49% (aLFA-1) and 68% (aCD2) greater than Dynabeads with comparable T cell products, preceded by elevated metabolic and transcriptional activity. Notably, while stiff substrates increased yield, soft substrates produced T cells with superior antigen-specific killing selectivity. These findings highlight the role of mechanical sensing in T cell-APC interactions and suggest improved manufacturing methods for adoptive T cell therapy (ACT).

  PublisherOA PDFDOI

• Uncovering Design and Assembly Rules for mRNA–DNA Origami

  Nano Letters · 2026-02-10

  articleOpen access

  mRNA-DNA hybrid origami enables integration of the RNA functionality into programmable DNA nanostructures, yet robust design and assembly rules remain lacking. Here, we systematically define parameters governing the high-yield formation of compact mRNA-DNA hybrid origami. Using mature mRNAs encoding firefly luciferase, enhanced green fluorescent protein (EGFP), and mCherry as scaffolds, we designed five architectures spanning varied sizes, shapes, crossover geometries, and packing densities. We identify asymmetric A-form crossovers, monovalent-cation-rich buffers, and moderate-temperature annealing as critical for suppressing RNA degradation and kinetic trapping while accommodating RNA-DNA helical geometry. Atomic force microscopy confirms monodisperse, well-folded nanostructures with nanoscale precision comparable to that of DNA origami. These results establish generalizable design rules and a standardized synthesis protocol for mRNA-DNA hybrid origami.

  PublisherOA PDFDOI

• Uncovering Design and Assembly Rules for mRNA–DNA Origami

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-09

  preprintOpen access

  Abstract mRNA–DNA hybrid origami offers a powerful route to combine the structural programmability of DNA origami with the biological functionality of messenger RNA, but generalizable design and assembly rules for these hybrids remain poorly defined. Here we systematically investigate the design principles and synthesis conditions that govern high-yield formation of mRNA–DNA hybrid nanostructures. Using mature mRNAs encoding firefly luciferase, EGFP, and mCherry as scaffolds, we construct a series of five hybrid compact origamis with diverse sizes, shapes, crossover strategies, and packing densities. We identify key parameters that control folding fidelity, including asymmetric A-form crossovers, monovalent-cation concentrations, and moderate-temperature annealing protocols, which together mitigate RNA instability, reduce kinetic traps, and accommodate RNA–DNA helical geometry. Atomic force microscopy reveals monodisperse, well-folded structures consistent with design expectations across most architectures and confirms that optimized conditions produce nanoscale precision comparable to DNA origami. Our findings establish generalizable design rules and a standard synthesis protocol for mRNA–DNA hybrid origami, providing a framework for their use in gene delivery and other RNA-based nanotechnologies.

  PublisherOA PDFDOI

• RNA nanotherapeutics with fibrosis overexpression and retention for MASH treatment

  Nature Communications · 2024-08-27 · 32 citations

  articleOpen access

  Metabolic dysfunction-associated steatohepatitis (MASH) poses challenges for targeted delivery and retention of therapeutic proteins due to excess extracellular matrix (ECM). Here we present a new approach to treat MASH, termed “Fibrosis overexpression and retention (FORT)”. In this strategy, we design (1) retinoid-derivative lipid nanoparticle (LNP) to enable enhanced mRNA overexpression in fibrotic regions, and (2) mRNA modifications which facilitate anchoring of therapeutic proteins in ECM. LNPs containing carboxyl-retinoids, rather than alcohol- or ester-retinoids, effectively deliver mRNA with over 10-fold enhancement of protein expression in fibrotic livers. The carboxyl-retinoid rearrangement on the LNP surface improves protein binding and membrane fusion. Therapeutic proteins are then engineered with an endogenous collagen-binding domain. These fusion proteins exhibit increased retention in fibrotic lesions and reduced systemic toxicity. In vivo, fibrosis-targeting LNPs encoding fusion proteins demonstrate superior therapeutic efficacy in three clinically relevant male-animal MASH models. This approach holds promise in fibrotic diseases unsuited for protein injection. Metabolic dysfunction-associated steatohepatitis (MASH) poses challenges for targeted delivery and retention of therapeutic proteins due to excess extracellular matrix (ECM). To address this, the authors developed a “Fibrosis Overexpression and Retention (FORT) strategy” that can improve mRNA expression in the fibrotic region and extend the expressed protein in situ.

  PublisherDOI

• RNA Nanotherapeutics with Fibrosis Overexpression and Retention (FORT) for NASH Treatment

  Research Square · 2024-01-30

  preprintOpen access
  PublisherOA PDFDOI

• The type 1 diabetes immune niche: Immunomodulatory biomaterial design considerations for beta cell transplant therapies

  Journal of Immunology and Regenerative Medicine · 2022-07-01 · 3 citations

  articleSenior authorCorresponding
  PublisherDOI

• List of contributors

  Elsevier eBooks · 2020-01-01

  book-chapter
  PublisherDOI

• Synergistic lipid compositions for albumin receptor mediated delivery of mRNA to the liver

  Nature Communications · 2020 · 327 citations

  • Chemistry
  • Cell biology
  • Biochemistry

  Lipid-like nanoparticles (LNPs) have potential as non-viral delivery systems for mRNA therapies. However, repeated administrations of LNPs may lead to accumulation of delivery materials and associated toxicity. To address this challenge, we have developed biodegradable lipids which improve LNPs clearance and reduce toxicity. We modify the backbone structure of Dlin-MC3-DMA by introducing alkyne and ester groups into the lipid tails. We evaluate the performance of these lipids when co-formulated with other amine containing lipid-like materials. We demonstrate that these formulations synergistically facilitate robust mRNA delivery with improved tolerability after single and repeated administrations. We further identify albumin-associated macropinocytosis and endocytosis as an ApoE-independent LNP cellular uptake pathway in the liver. Separately, the inclusion of alkyne lipids significantly increases membrane fusion to enhance mRNA release, leading to synergistic improvement of mRNA delivery. We believe that the rational design of LNPs with multiple amine-lipids increases the material space for mRNA delivery.

  PublisherOA PDFDOI

• Magnetic Retrieval of Encapsulated Beta Cell Transplants from Diabetic Mice Using Dual‐Function MRI Visible and Retrievable Microcapsules

  Advanced Materials · 2020 · 18 citations

  1st authorCorresponding
  • Materials science
  • Biomedical engineering
  • Nanotechnology

  Encapsulated beta cell transplantation offers a potential cure for a subset of diabetic patients. Once transplanted, beta cell grafts can help to restore glycemic control; however, locating and retrieving cells in the event of graft failure may pose a surgical challenge. Here, a dual-function nanoparticle-loaded hydrogel microcapsule is developed that enables graft retrieval under an applied magnetic field. Additionally, this system facilitates graft localization via magnetic resonance imaging (MRI), and graft isolation from the immune system. Iron oxide nanoparticles encapsulated within alginate hydrogel capsules containing viable islets are transplanted and the in vitro and in vivo retrieval of capsules containing nanoparticles functionalized with various ligands are compared. Capsules containing islets co-encapsulated with COOH-coated nanoparticles restore normal glycemia in immunocompetent diabetic mice for at least 6 weeks, can be visualized using MRI, and are retrievable in a magnetic field. Application of a magnetic field for 90 s via a magnetically assisted retrieval device facilitates rapid retrieval of up to 94% (±3.1%) of the transplant volume 24 h after surgical implantation. This strategy aids monitoring of cell-capsule locations in vivo, facilitates graft removal at the end of the transplant lifetime, and may be applicable to many encapsulated cell transplant systems.

  PublisherOA PDFDOI

• Challenges in the development of immunoisolation devices

  Elsevier eBooks · 2020-01-01

  book-chapter
  PublisherDOI

Frequent coauthors

• Yifan Ge

  Boston VA Research Institute

  25 shared

• Wenzhe Li

  Shenyang Pharmaceutical University

  24 shared

• Xueguang Lu

  Peking University

  24 shared

• Yuxiu Liu

  Dalian Institute of Chemical Physics

  23 shared

• Wei Liu

  Dalian Institute of Chemical Physics

  23 shared

• Chenlong Wei

  Bioscience (China)

  23 shared

• Yizhe Xue

  King University

  23 shared

• Róbert Langer

  Massachusetts Institute of Technology

  23 shared

Education

• MChem with a Year in Industry, Chemistry

  University of York

• PhD DIC, Materials, Bioengineering (Faculty of Engineering)

  Imperial College London

Awards & honors

• Fellowship, Berkeley Space Center