The Vector

Editorial Team

Karen Bulaklak, PhD – Editor, The Vector
Jon Brudvig, PhD – Associate Editor, The Vector
Jessica Schneller, PhD – Junior Editor, The Vector

Inside This Issue

Leadership Message
Breaking Through
From Molecular Therapy
Society News
Career Center
Public Policy
Industry News

Leadership Message

#ASGCT23 Starts Next Week!

Hello, ASGCT members,

I hope you’re all as excited as I am for next week’s 26th Annual Meeting! I’m really looking forward to seeing many of you in person in Los Angeles and virtually for what has already become another record-breaking event.  This year we accepted more than 1,650 abstracts—34% more than last year—and I hope you’re ready to learn from all the research in our largest collection yet. Check out our searchable abstracts module here or you can download a PDF version. If you’re available the first morning of the meeting, May 16, please consider registering for one of our seven excellent Workshops. During workshops, speakers will provide more in-depth examinations of topics in CGT, like immune effector cells, as well as career-focused topics, like becoming a site for AAV gene therapy trials. Learn more about Workshops here and make sure you’re registered for the meeting if you’d like to add one to your schedule.

I have had such a wonderful year serving as ASGCT president and I want to thank all of you for being a part of that. Together, we returned to in-person meetings, created and planned more programming, launched our first podcast and new awards, expanded our global outreach, and much more. One upcoming event I’d like to note is our first Spotlight on Immuno-Oncology conference in August. During that event, we’ll discuss cancer treatment strategies that go beyond CART cells and the ways in which technologies developed by our members continue to advance treatments for cancer and other genetic disorders and infectious diseases. I’m so appreciative of all of the work done this year by our Board, all of our members and committees, and ASGCT staff, to further the field and our organization. I’d also like to warmly welcome our newest Board members who take office on June 1; I’m very excited to see what you all can accomplish and I’m confident the Board is in great hands moving forward.

That brings me to introducing our incoming president, my colleague Jeffrey Chamberlain, PhD! Dr. Chamberlain is a professor and the McCaw Chair in Muscular Dystrophy at the University of Washington. His career has focused on muscle biology, diseases, and therapeutics. Notably, his lab was the first to show that AAV could be used for systemic gene delivery to muscle. I’ve worked with Dr. Chamberlain closely, especially over the last year, and I have no doubt he’ll be a great leader for ASGCT.

Thank you again for everything, and I’ll see you next week. Enjoy the 26th Annual Meeting!



Hans-Peter Kiem, MD, PhD
ASGCT President


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Breaking Through

Protein expression/secretion boost by a novel unique 21-mer cis-regulatory motif (Exin21) via mRNA stabilization

Zhu Y, Saribas AS, Liu J, Lin Y, Bodnar B, Zhao R, Guo Q, Ting J, Wei Z, Ellis A, Li F, Wang X, Yang X, Wang H, Ho, WZ, Yang L, Hu


Summary by Jessica Schneller, PhD

The ability to manufacture recombinant proteins in mammalian cells at large scale is critical for large-scale production of vectors for gene and cell therapy, in addition to the study of the SARS-CoV-2 virus. Study of the SARS-CoV-2 spike (S) protein, which is an ideal target for vaccine research and a major inducer of neutralizing antibodies, has been hampered by low expression in mammalian cells. Despite decades of research into vector design, cell line engineering, and bioprocess optimization, certain proteins can only be expressed in mammalian systems at very low levels, compared to E. coli expression systems. The need therefore remains to identify methods for increasing protein production while maintaining low costs. In this study by Zhu et al, the authors identify a unique 21-mer oligonucleotide, designated Exin21, which was capable of significantly increasing the expression and secretion of both viral and non-viral proteins, including critical SARS-CoV-2 proteins. Exin21 encodes a polypeptide designated Qα, which was shown to increase production of various proteins including SARS-CoV-2 spike & membrane proteins as well as SARS-CoV-2 accessory proteins, endogenous human interleukin-2 (IL-2) & interferon-ℽ (IFN- ℽ), and anti-SARS-CoV-2 monoclonal antibodies (mAb). Exin21 also improved SARS-CoV-2 pseudovirus and lentivirus packaging and improved mRNA synthesis & stability. Exin21/Qα may therefore have the potential to be widely applied in the production of therapeutic proteins, antibodies, and mRNA vaccines.

Exin21/Qα was fortuitously identified during screening of positive clones for a dual-reporter system, in which Gaussia-Dura luciferase (gdLuc) and destabilized GFP (dsGFP) were fused onto the C terminus of the SARS-CoV-2 envelope (E) protein. The clone containing the Exin21/Qα heptapeptide sequence exhibited >20-fold higher luciferase activity than a clone not containing the polypeptide sequence. The ability of the Qα sequence to boost protein expression was further validated in transfection experiments using a vector expressing secreted embryonic alkaline phosphatase (SEAP) or Cypridina luciferase (cLuc). Qα was able to boost the production of all SARS-CoV-2 proteins and accessory proteins tested in mammalian cells, with increases in efficiency ranging from 3x - ~3,900x depending on the protein. Mutation assays used to determine the role of individual amino acid residues in Qα function validated that each residue of the heptapeptide was critical for boosting activity, and that the boosting activity itself was derived from the RNA structure of the 21-mer oligonucleotide motif.

To identify further applications of Exin21/Qα boosting of protein expression and production, similar assays were performed for non-viral proteins such as mouse NIBP and human ACE2, as well as human cytokines IL-2 & IFN- ℽ. Exin21/Qα maintained protein boosting expression & production in various cell types (HEK293T, HeLa, BHK). Exin21/Qα insertion into the C-terminus of the heavy and light chains of the human anti-SARS-CoV-2 monoclonal antibody boosted expression of mAb by up to 37-fold. To determine if the Exin21/Qα could boost packaging efficiency of the SARS-CoV-2 spike (S) protein in a pseudo typed lentivirus-like particle, Exin21/Qα was added to the C-terminal end of a codon-optimized SARS-CoV-2 S protein (Sd18) and shown to increase packaging capacity by up to 4x in HEK-hACE2 cells. Exin21/Qα additionally increased packaging capacity of Sd18 (Sd18Q) when used with a dual-reporter lentiviral (LV) transfer vector.

Exin21/Qα addition to lentiviral packaging proteins Pol and RRE boosted LV packaging of transfer vectors, an application which would be beneficial in the development of lentiviral vectors for gene therapy applications. Since a critical application of the Exin21/Qα heptapeptide would be to increase large-scale vaccine production yields, specifically for SARS-CoV-2, the authors sought to determine that Exin21/Qα might boost production of viral proteins after mRNA transfection in HEK293T cells. Exin21/Qα significantly increased the production of SARS-CoV-2 S protein in a time- and dose- dependent manner, and this was also applicable in production of SARS-CoV-2 nucleocapsid and envelope proteins. Exin21/Qα increased the half-life of the encoded mRNAs of both viral envelope and spike proteins by up to 6-fold, and was demonstrated to significantly increase mRNA synthesis, mRNA stability, and possibly translational efficiency. To establish that Exin21/Qα could boost protein secretion as well as expression, protein levels in cell culture supernatant were measured after transfection of the dual-reporter expression vector containing Exin21/Qα and shown to increase targeted protein expression in the supernatant.

These studies confirm the identity and activity of a novel regulatory motif, Exin21/Qα, capable of boosting targeted protein expression and secretion. Exin21 contains a unique and exclusive composition of 21 nucleotides; that is relatively small and does not contain cellular or viral genes. Exin21 addition to mRNA was able to increase protein expression and secretion, and was applicable to different types of proteins including viral, non-viral, intracellular, structural, and secretory proteins. Exin21/Qα critically can enhance production of recombinant proteins in mammalian cells, which should have versatile application in biomedical research and biotechnological industry.           

From Molecular Therapy

Special issue call for papers: Biomanufacturing in gene and cell therapy
Submit to a special issue of Molecular Therapy—Methods and Clinical Development by May 31! The issue will be dedicated to all aspects of preclinical and clinical manufacturing of gene and cell therapy products. Learn more and submit today!

Latest MT issues: Check out the most recent issues of these Molecular Therapy family journals:


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Society News

Introducing Our Five Newest Board Members

Please welcome these new members of the ASGCT Board of Directors, who will take office on June 1! Congratulations to Terry Flotte, MD; Federico Mingozzi, PhD; Punam Malik, MD; Daniel Bauer, MD, PhD; and Kah-Whye Peng, PhD. Learn more about them on our blog.

New Award Recipients Honored for Service, Advancing DEI, Mentorship

We're proud to announce the winners of three brand-new Annual Meeting awards! During next week's meeting, we'll be honoring Kenneth Cornetta, MD (Exemplary Service Award); Rayne Rouce, MD (Award for Excellence in Advancing Diversity, Equity, and Inclusion); and Stuart Orkin, MD (George Stamatoyannopoulos Mentorship Award). Watch them accept their awards on Friday, May 19, at 1:30 p.m. (PT).

Submit Cancer Immunotherapy Abstracts Through June 2

Are you conducting research in immuno-oncology? Send it to us for the chance to present your work Aug. 1-2 at the hybrid Spotlight on Immuno-Oncology conference. Submit an abstract on CAR designs, B-cell malignancies, and more, by noon (CT) on June 2.


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Career Center

Are you looking for a job in the field of gene and cell therapy? Check out the new ASGCT Career Center for great opportunities with industry, government, and academic organizations. Sign up to receive alerts for open jobs in your area.

If you're from a recruiting institution, advertise in the Featured Jobs section to target the 5,000+ audience of The Vector.

Featured Jobs


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Public Policy

Potency Assay White Paper Details Challenges for Regulators and Developers 

The development of potency assays for cell and gene therapies (CGTs) presents significant challenges. Regulators require developers to measure the potency of biologics to ensure that a consistent product is delivered to all patients; doing so requires a significant upfront investment from developers, and regulatory delays are common due to the complex nature and evolving scientific understanding of both the methods used to demonstrate potency and the underlying CGT products themselves.  

To address this issue, ASGCT and the Alliance for Regenerative Medicine (ARM) held a roundtable involving FDA regulators, developers, and other stakeholders to discuss development and validation of potency assays for CGTs. Participants at the roundtable expressed a desire for faster and more robust communication from FDA and noted the importance of investing in potency and product consistency across clinical phases. A newly released white paper outlines key challenges faced by both the Agency and developers when navigating the regulatory process for potency assays. ASGCT is grateful to all who participated in the critical solution-seeking discussions at the roundtable. 

Society Thanks Volunteers, Legislators for Engaging on CGT Challenges 

The commitment to advancing the field of cell and gene therapy (CGT) was on display during a series of meetings with legislators on Capitol Hill April 19-20. Society members spoke with a bipartisan group of U.S. representatives and senators about a variety of topics related to CGT, including the challenges involved in manufacturing and clinical development and the complexities of reimbursement and patient access. The transformative nature of CGTs and paradigm-shifting implications for patients were especially highlighted. 

These meetings showcased the vast potential of CGTs in treating a range of diseases and disorders. The Society is helping to shape policy that supports patient access to these life-changing therapies. ASGCT looks forward to continued engagement with policymakers on these important issues, and thanks its member volunteers for their participation in the meetings: 

  • Hans-Peter Kiem, ASGCT President + Director, Stem Cell and Gene Therapy Program, Clinical Research Division, Fred Hutch Cancer Center  

  • Jennifer Wellman, Chief Operating Officer, Akouos  

  • Rayne Rouce, MD, Associate Professor, Department of Pediatrics section on Hematology-Oncology, Baylor College of Medicine 

  • Maritza McIntyre, PhD, President, Advanced Therapies Partners LLC 

  • Francesca Cook, MPH, Vice President, Market Access, REGENXBIO 

Industry News

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May 7-11, 2024 | Baltimore, MD

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