The Vector

Volume 8, Issue 5: May 2019

Editorial Team

Melvin Rincon, MD, PhD – Editor, The Vector
Edith Pfister, PhD – Associate Editor, The Vector

Inside This Issue

Leadership Message
Breaking Through
Society News
Public Policy
Industry News



President's Message

The Case For Growth

In my first message to the ASGCT membership as president of the Society, I want to thank the more than 4,700 attendees at the ASGCT 22nd Annual Meeting last week. I would also like to personally thank Dr. Michele Calos for her fantastic work as ASGCT President throughout the past year and to commend her for planning a wonderful Annual Meeting under challenging circumstances.

As many of you know, the growth and enthusiasm surrounding our field has surpassed even our most optimistic expectations. Though we experienced some growing pains related to the crowds we drew and the space available to us in the hotel, I recognize the need for ASGCT to expand and cannot wait to share news about our space for the 2020 Annual Meeting, the Hynes Convention Center in Boston. I also want to take a moment to express my deep gratitude to the ASGCT staff for their long hours, hard work, and overall accomplishment in managing the Annual Meeting and the difficulties that came with the growth of the event. This is an exciting moment, and one we choose to greet as an opportunity to welcome interest from industry, support our young investigators, advocate for the work of our members, and make this incredible growth sustainable for years to come.

The increase in industry representation at the Annual Meeting during the past two years has been impressive, but not entirely surprising. The groundbreaking translational work from ASGCT members has brought attention to the promise of our field from around the world. As I read from one of our members quoted in a news story from the Annual Meeting, “there is no disease off the table.”

I welcome biotech companies and investors to this and all future ASGCT Annual Meetings and look forward to developing tools and services to best facilitate their connection with our members’ research.

To help with those connections, ASGCT opens applications for our second year of Career Development Grants on June 1. All told, we will distribute $300,000 to associate members working to advance their careers towards independence. You’ll also be hearing more about the upcoming ASGCT Policy Summit. ASGCT will lead the way in legislative, global regulatory, and genomic ethics discussions over three full days of meetings this November.

Finally, I’m excited to begin announcing the results of the 2019 strategic plan. Following a number of committee discussions and the in-person board of directors meeting at the Annual Meeting, the Strategic Planning Committee has developed a three-year vision to establish ASGCT as a leading voice in the scientific community. With this plan, I fully expect our meteoric rise to continue sustainably and for the foreseeable future. I’m excited and honored to lead this inspiring group of scientists into the 23rd Annual Meeting in the heart of the biotech valley of Boston, our return to the sprawling space of a convention center, and to see this Society truly spread its wings in 2020.

With gratitude,
Guangping Gao, Ph.D.



Breaking Through

ASGCT 22nd Annual Meeting Recap

By Edith Pfister, Ph.D.

I always feel a combination of excitement and nervousness leading up to conferences, especially if I’m speaking. I’m excited for all I’ll learn, but I’ve never really managed to avoid feeling anxious about standing up and presenting in front of an audience. Will I remember to say what I meant to? Will I get questions that I can’t answer? Will I fall on my face on the way to the podium? (That has never happened to me, but still I worry). Now that the ASGCT 22nd Annual Meeting is over, I feel comfortable calling the event a success.  I’ve only been attending for a few years, but even in that short time, I feel like there has been a clear shift toward more advanced pre-clinical and clinical programs. This is exciting because it means that gene therapies are getting to people who need them. Meanwhile there were still a good number of innovative new approaches which I look forward to following in the future.

Monday morning featured abstract sessions and a session on pricing and access. This session brought together different perspectives to continue a discussion that I became aware of with the release by ASGCT last year of the white paper, Addressing the Value of Gene Therapy: Enhancing Patient Access to Transformative Treatments. As gene therapy continues to advance to the clinic, many more people are becoming interested in and have a stake in these issues, so it is nice to see the discussion continuing.

The “Gene Silencing Approaches” session featured different approaches to gene silencing including Zinc Finger proteins to reduce Tau and to achieve allele-specific reductions in mutant Huntingtin as well as AAV gene therapy to deliver RNAi to various regions of the CNS. Dr. Ornit Chiba-Falek presented an interesting talk on epigenomic targeting of α-synuclein (SNCA) in Parkinson’s disease (PD). Her group has developed a lentiviral vector to deliver dCas9 fused to DNA (cytosine-5)-methyltransferase 3A (DNMT3A) and a guide RNA targeting a CpG island in intron 1 of the α-synuclein gene. Hypomethylation of this CpG island has been shown in the brains of patients with PD and Lewy body dementia, and its demethylation upregulates SNCA expression. Using their targeted DNMT3A, they were able to show increased methylation within the intron 1 CpG region and a 30% reduction in SNCA mRNA and protein.

On Tuesday in a session entitled "How-to" - Design, Delivery, and Application of RNA Therapeutics, Dr. Christopher Alabi presented a beautiful talk explaining design considerations, synthesis and potential of antibody nucleic acid conjugates, focusing on the delivery of RNAi via antibody-siRNA conjugates.

Dr. Michel Sadelain delivered the George Stamatoyannopoulos Memorial Lecture, elucidating the history, mechanisms and challenges of CAR T cell therapy. Why and how do some cancer cells escape engineered CAR-T cells and what causes T cell exhaustion?

In the Outstanding New Investigator session, Dr. Steven Gray described his effort to bring gene therapy for giant axonal neuropathy to pediatric patients and how the activity of patient advocacy groups which led to its fruition. Dr. Anna Kajaste-Rudnitski presented work on engineering of human hematopoietic stem cells focusing on how Cyclosporine H (CsH) can improve lentiviral gene transfer by inhibiting interferon-induced transmembrane protein 3 (IFITM3) and limiting the innate immune response.

On Wednesday, the Sonia Skarlatos public achievement award was presented to the Muscular Dystrophy association, acknowledging the important role that patients and patient advocacy groups play in our work. The outstanding achievement lecture was presented for Dr. John J. Rossi by his son. Before the discovery of RNAi, Dr. Rossi was developing antiviral ribozymes and antisense oligonucleotides targeting HIV. He pioneered the practice of expressing RNA molecules such as antisense RNAs and hairpins in the nucleus. He described his extensive studies using both chemically synthesized and expressed siRNA to induce RNAi.  Finally, he touched on the recent discovery and development of activating small RNAs (RNAa), which extends the RNA toolkit, allowing both positive and negative regulation of genes.

The Presidential symposium featured Dr. George Church, who was funny and engaging. He described methods for limiting the immune response to viral vectors. Although the immune response to AAVs is generally believed to be minimal, he made the case that limiting the immune response could simultaneously improve the safety and effectiveness of gene therapy vectors. He described an oligonucleotide sequence, “io2”, derived from telomeres, which appears to limit the TLR9-mediated response to AAV and improves transduction efficiency. In addition, Dr. Church described a machine learning platform for AAV engineering and the detection, using this platform of a previously unidentified gene that is conserved in multiple AAV serotypes.

Finally, the presentation of top abstracts featured the presentation by Dr. Perry Shieh on Audentes Therapeutics’ ASPIRO Phase I/II clinical trial of gene therapy for X-linked Myotubular Myopathy (XLMTM). The clinical vector in this study is an rAAV8 designed to deliver functional copy of the myotubularin gene to muscle. In what I’m sure was a highlight of the meeting for many of us, he showed videos of boys who before treatment could not sit or breathe on their own sitting up, smiling and laughing. I will admit that I was brought to tears by his presentation. He reported that 3 out of the 8 patients who received the treatment were completely off the ventilator and all had improved respiratory function. In contrast to what would be expected given the natural history of the disease, all patients were sitting without support and 3 patients were crawling or standing with support.

Thursday the meeting wrapped up with a few more abstract sessions. I stayed until the end, as my presentation was in the last session. After a last-minute panic correction of my slides, I managed to convince myself that I was excited, rather than nervous and celebrated the talks of a few colleagues who were also scheduled on the last day, wrapping up what was an enjoyable and informative meeting.

Society News

Call for Applications: Junior Editor, The Vector

ASGCT is looking for a new junior editor to join The Vector's editorial team. The junior editor serves a one year term, appointed every year by the ASGCT Publications Committee. Candidates are asked to submit a CV, statement of interest, and 500 word summary of this article. At the conclusion of the junior editor's term, the successful volunteer is expected to ascend to the position of associate editor and, ultimately, editor.

The roles and responsibilities are as follows:

  • Coordinate with ASGCT staff and the editors to solicit scientific content and summaries for Breaking Through section of The Vector
  • Review and edit scientific summaries before they are added to The Vector
  • Participate on planning conference calls with the Editors and ASGCT staff

If you are interested in serving as the junior editor or have any questions, please send your CV, a brief statement of interest, and a 500 word summary of this article to Alex Wendland, ASGCT digital communications manager.

ASGCT Closes Record-Breaking Annual Meeting

More than 4,700 attendees filled the halls and sessions rooms of the Washington Hilton from April 29 – May 2 to attend the ASGCT 22nd Annual Meeting. The Society would like to thank all of members who attended the Annual Meeting for their patience and understanding regarding session room overflow.

The 23rd Annual Meeting, May 12 – 15, 2020, will mark ASGCT's return to a convention center and all of the additional space considerations that come with a venue the size of Boston's Hynes Convention Center. We can't wait to visit the Bio Valley in Boston next year!

Public Policy

Scientific Leaders Call for Global Moratorium on Germline Gene Editing

A group of more than 60 scientific leaders, bioethicists, and biotechnology executives, including past-presidents and current board of directors members from ASGCT, signed on to a letter to Health and Human Services Secretary Alex Azar last month, calling for a binding moratorium on clinical germline gene editing until serious concerns are addressed. These leaders find Dr. Jiankui He’s reported actions in November involving clinical use of germline gene editing to be currently irresponsible and to carry serious problems which have no scientific, ethical, or societal consensuses. To fully address these concerns, the letter calls for the Administration to convene all stakeholders, including members of the scientific, medical, patient, caregiver, policy, legal, ethical, and faith communities. The signatories also support effective and easily accessible mechanisms for reporting potential violations.

The letter indicates that regulatory agencies are well positioned to oversee future trials of therapeutic gene editing of somatic cells, and consider it unlikely that somatic cell gene editing will give rise to new or unique ethical concerns substantially different from those associated with other forms of therapeutics that have already been well discussed. Watch your email in the coming weeks for instructions from ASGCT on how to add your name to support the letter’s positions.

Read The Full Letter

Streamlining Gene Therapy Oversight

The National Institutes of Health (NIH) Office of Science Policy (OSP), in conjunction with the Food and Drug Administration (FDA), finalized its proposal to amend the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines) on April 25. "ASGCT is pleased with the NIH proposal to eliminate Recombinant DNA Advisory Committee’s (RAC) review and reporting requirements for human gene therapy protocols,” stated ASGCT President Michele Calos. “Doing so will eliminate substantial duplication of effort, which could have led to unnecessary delays in the approvals of gene therapies.”

ASGCT’s comments last fall in support of the proposed amendments reflect the Society’s prioritization of expeditious development of safe and effective gene therapies, due to their potential to positively affect the lives of patients with serious, potentially fatal diseases. The RAC, renamed the Novel and Exceptional Technology and Research Advisory Committee (NExTRAC), will now advise the NIH director on the scientific, safety, and ethical issues associated with all emerging biotechnology.

Dr. Jessica Tucker, Director of Biosafety, Biosecurity, and Emerging Biotechnology at the OSP, provided a keynote address on the topic as part of a pre-meeting workshop leading into the ASGCT’s Annual Meeting last week. ASGCT will continue to provide details to those in the field regarding how these changes to the NIH Guidelines will affect gene therapy review and reporting processes.

Industry News

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