Delivering genes and receiving honors – Q&A with Angela Pannier

Presidential Early Career awardee Prof Angela Pannier tells us about her research on finding safer and efficient methods of gene delivery, as well as her thoughts on receiving her prestigious US government honor.

Gene and cell therapies are seeing a resurgence, with an acceleration in scientific innovation and renewed interest in how they should benefit society. Whilst the potential biomedical applications may seem limitless, there remain many technical obstacles and safety issues to overcome. Professor Angela Pannier of the University of Nebraska tells us about her research in this area, with a focus on non-viral methods of gene delivery, that she recently reviewed in Journal of Biological Engineering.

Q: Could you briefly describe your research interests?

A: Our lab is interested in engineering biomaterials (matrices, interfaces, and delivery vectors) and cellular systems for various applications – including gene therapy, tissue engineering, developmental biology models, medical devices, medical diagnostics, and vaccination therapies – to dramatically improve health outcomes.  In particular we are interested in studying and developing methods to enhance nonviral gene delivery, using molecular profiling, mathematical modeling, and priming strategies (both chemical and physical) to uncover new insights into the “biology of transfection”; our studies have enabled the development of new strategies to significantly improve gene transfer into adult stem cells.  We have also pioneered the use of zein, a protein from corn, for oral DNA delivery.  In addition, we work in the field of tissue engineering, uniquely using principles from that field to form models of developmental biology, including porcine embryonic development and cartilage growth.

Q: Could you explain the need for and potential applications of gene delivery?

Gene delivery has the potential to profoundly impact medicine and biotechnology through: i) therapeutics to correct genetic deficiencies, from hereditary single-gene defects like cystic fibrosis and hemophilia, to  cell therapies to treat cancer, cardiovascular disease, neurodegenerative disorders, or infectious disease; ii) diagnostics, biotechnological assays, and functional genomics to determine gene function or expression in clinical and research settings; iii) medical devices to improve implant functionality and integration (e.g. gene-eluting stents); iv) vaccination to produce a robust immune response; and v) regenerative medicine and tissue engineering, where gene delivery can present chemical factors to guide tissue formation or response to injury, for treatment of organ loss and failure, or to aid in the survival of a transplanted organ.

A: How do we deliver genes to the cells and tissues that need them?

There are two main pathways to achieve delivery of genes or nucleic acids into cells:  viral delivery or nonviral delivery.  The former, viral delivery, makes use of engineered viral particles to efficiently transfer the genetic cargo into cells.  Nonviral techniques typically use chemical carriers (e.g. polymer or lipid materials) or physical strategies (e.g. ultrasound or gene gun) to deliver the genes.

Q: You specialize in non-viral methods of gene delivery. What are the major strengths (and weaknesses) of this approach compared to others?

A: Viral gene delivery, while highly efficient in stem cells (including those derived from fat and bone marrow, which my lab is especially interested in) and other cells, is limited by safety issues, including insertional mutagenicity. Even with viral vectors that do not integrate, safety risks of viral transduction in the manufacture of cell therapies remain, due to possible presentation of viral antigens on transduced cells that could potentially activate an immune response in vivo following transplantation. In addition, viruses are limited by transgene cargo capacity, and difficulty in production and scale-up. These safety risks and manufacturing challenges motivate our focus on the development of methods for efficient nonviral gene delivery. Nonviral gene delivery methods can be safer than viral methods, and are more scalable and flexible, but are less efficient.

Q: What challenges or obstacles still remain in relation to this line of research?

A: I like to say there are three challenges with our field:  delivery, delivery and delivery.  But in all seriousness, our major challenges are achieving safe (non-immunogenic and non-toxic) and efficient (targeted and at appropriate levels) delivery of the genetic cargo.

I like to say there are three challenges with our field:  delivery, delivery and delivery.

Q: Are there any other developments in the field we should look out for?

A: Our field is in a time of revival and intense and immense excitement!  With FDA approved gene therapies now available to patients, as well as CAR-T therapy which makes use of gene delivery for production of the T-cells, the time of gene and cell therapies is now!  We next need to think about how to finance and fund these therapies, which are proving to be very costly.

Q: Many congratulations on your Presidential Early Career Award for Scientists and Engineers (PECASE). What was your reaction to the announcement?

A: I was honestly shocked and then so humbled and grateful!  What an honor this is… an award that you do not apply for… in fact I was awarded it based on a nomination from NIBIB/NIH from 2017, so I had no idea I was even being considered!  While I received the award, it really represents so much more than just me…it is an award that celebrates the work and support of my fantastic lab members (past and current) and my institution!

You can read more on non-viral gene delivery methods in Angela Pannier’s Review article, part of a collection in Journal of Biological Engineering with contributions from Emerging leaders in biological engineering.


Angela K. Pannier, Ph.D. is a Professor and Biomedical Engineer in the Department of Biological Systems Engineering at the University of Nebraska-Lincoln (UNL), with a Courtesy Appointment in the Department of Surgery and the Mary and Dick Holland Regenerative Medicine Program at the University of Nebraska Medical Center (UNMC).A highly funded researcher, Dr. Pannier has been a primary investigator on 10 projects, published over 45 manuscripts, 3 book chapters, more than 85 conference proceedings/abstracts and 2 patents. She has been very successful in basic research funding (e.g. AHA Scientist Development Grant, NSF CAREER, NSF MRI) and industry funding (JA Woollam Co., and others), but has also been successful at translating her work to agricultural applications and research funding (USDA AFRI). Dr. Pannier was awarded the NIH Director’s New Innovator Award (DP2) in 2017 for her pioneering work in gene delivery, and is the first Nebraskan to ever earn this honor.In 2017 she worked as a visiting scholar at the Leibniz-Institut für Polymerforschung in Dresden, Germany. Dr. Pannier has proudly mentored 14 graduate students and over 45 undergraduate students in her lab; she currently is mentoring 7 graduate students and 4 undergraduate students. Dr. Pannier has served as the Biomaterials Track Chair for the 2017 Biomedical Engineering Society Annual Meeting, and is a current member of the Nanoagents & Synthetic Formulations Committee for the American Society of Gene and Cell Therapy.She has also been active in the American Institute of Chemical Engineers, Institute of Biological Engineering, and the Society of Women Engineers. Dr. Pannier serves on the editorial board for Experimental Biology and Medicine and Regenerative Medicine Frontiers.In 2019 Dr. Pannier was awarded a Presidential Early Career Award for Scientists and Engineers (PECASE) for 2017.

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