The Vector

Volume 8, Issue 9: September 2019

Editorial Team

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

Inside This Issue

Leadership Message
Breaking Through
Society News
Career Center
Public Policy
Industry News



Leadership Message

ASGCT’s Role in Treating Sickle Cell Disease

Sub-Saharan Africa is home to 70 percent of children who live with sickle cell disease (SCD) worldwide, a painful inherited disorder that affects red blood cells. More than 90 percent of children with SCD in resource-poor countries do not survive into adulthood, and many die before they turn five. 

September is Sickle Cell Awareness Month, and a major goal of ASGCT’s new strategic plan is to expand our outreach to countries outside the U.S. In the years ahead, we plan to identify more opportunities to promote and help increase access to gene and cell therapies, especially for patients in developing nations. 

Gene and cell therapies can help enhance the lives of patients living with SCD, and ongoing clinical trials are currently testing these modalities throughout the U.S. However, we need to expand our reach so that the most current information and access to potential treatments can get to the patients that need them.

To help these patients, we plan to engage researchers, health care providers, commercial entities, and professional societies outside of the U.S. in order to bring together as much scientific and educational programming as possible. We will establish new international partnerships and strengthen existing ones. Through our sponsorship of the Foundation for the National Institutes of Health’s International Summit in Human Genetics and Genomics, we are supporting the building of infrastructure and genetic technologies in low- and middle-income countries.

We also want to facilitate increased understanding of the global regulatory landscape, in part through our Policy Summit, so we are able to help advance gene and cell therapies outside of the U.S. We believe that collaborating in research, funding, and outreach efforts will move us toward the goal of achieving equitable access to gene therapy treatments for patients in developing nations.

ASGCT also continues to educate the public about sickle cell disease and other inherited blood disorders. The videos and infographics on the Patient Education section of our website provide dynamic, engaging resources for patients and the public to learn about how these disorders affect the human body and, and read about how gene therapy can help treat them. Through these efforts we hope to help bridge the gap between SCD patients and necessary treatments.


Guangping Gao, Ph.D.
ASGCT President


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Breaking Through

AAV-PHP.B Administration Results in a Differential Pattern of CNS Biodistribution in Non-human Primates Compared with Mice

Liguore WA, Domire JS, Button D, Wang Y, Dufour BD, Srinivasan S, McBride JL.


Summary by Edith Pfister, Ph.D.

Disorders of the central nervous system have long defied the efforts of scientists to develop effective treatments. This is due both to the complex nature of these diseases and to the particular problems associated with reaching the affected structures.

Neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease and Huntington’s disease affect structures deep within the brain. Treatments delivered systemically must be able to penetrate the blood brain barrier and be able to penetrate deep into the brain parenchyma. New methods of capsid library generation and screening led to much hope that AAVs would be able to overcome these barriers, and even be able to be tailored to deliver their cargo with precision to the areas of need.

Indeed, using an evolutionary approach, Deverman et al. generated a novel AAV9 based capsid AAV-PHP.B which shows broad brain distribution following systemic delivery1. Some consternation followed when it seemed that this capsid exhibited the desirable behavior only in one strain of mice, or only in some strains of mice, or only in mice (you’d be forgiven for not knowing which, as it was a fast moving target) which initially left the future clinical relevance of this vector unknown.

This uncertainty has recently been cleared with the publication, by multiple groups, of an isoform of the Ly6a gene which is responsible for the blood brain barrier penetrating properties of AAV-PHP.B2,3. Liguore et al. have just provided an additional layer of complexity to this question. They show that in NHPs, unlike in mice, the route of delivery matters. In C57/BL6 mice, delivery to the jugular vein, carotid vein, lateral ventricle and cisterna magna, all produce roughly the same distribution (with the exception of better delivery to the striatum in the group injected in the lateral ventrical).

In contrast, in Rhesus macaque, delivery into the cisterna magna appeared superior to delivery to the carotid artery. It seems likely that multiple factors are in play here: differences in the natural tropism of the capsid in mice vs. Rhesus macaque may interact with differences in brain size, body size, and CSF flow to produce dramatic differences in vector biodistribution.

Happily, for patients who are waiting for novel methods to treat the diseases affecting deep brain structures, the research is continuing to progress rapidly.

1.           Deverman, B. E. et al. Cre-dependent selection yields AAV variants for widespread gene transfer to the adult brain. Nat. Biotechnol. 34, 204–209 (2016).

2.           Hordeaux, J. et al. The GPI-Linked Protein LY6A Drives AAV-PHP.B Transport across the Blood-Brain Barrier. Mol. Ther. 27, 912–921 (2019).

3.           Huang, Qin, et al. Delivering genes across the blood-brain barrier: LY6A, a novel cellular receptor for AAV-PHP. B capsids. bioRxiv (2019): 538421.



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Society News

NIH Director Collins to Speak at ASGCT Policy Summit

Francis Collins, M.D., Ph.D., director of the National Institutes of Health (NIH) and a physician-geneticist, delivers his keynote address, “The Need for an International Moratorium on Clinical Uses of Human Germline Gene Editing,” at the ASGCT Policy Summit on November 6 at The Westin in Washington, D.C. For more details on Dr. Collins' keynote address, and to view the full agendas on each day of the Summit, visit this section of our website.

2020 Annual Meeting Website is Now Live

For the most up-to-date information on our upcoming Annual Meeting, you can now visit! Along with the launch of the Annual Meeting website, the Society is excited to announce the plenary speakers, so visit the website for more information.



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Career Center—NEW!

Recruit and connect with top gene and cell therapy job seekers on the ASGCT Job Bank.

Advertising opportunities are also available monthly via the Featured Jobs section and allow recruiting institutions to target the 3,000+ audience of The Vector.

Featured Jobs


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Public Policy

ASGCT Submits Comments on Clinical Germline Gene Editing

ASGCT submitted comments to two groups working on the issue of clinical use of germline gene editing. The first set of comments [PDF 1] was sent to the World Health Organization’s (WHO) Advisory Committee on Developing Global Standards for Governance and Oversight of Human Genome Editing. The second set of feedback was on Senate Resolution 275, introduced by Senators Diane Feinstein, Jack Reed, and Marco Rubio to call for international ethical standards in genome editing research. In both comments, ASGCT stressed the importance of inclusive processes that reflect diverse stakeholders and their views. ASGCT also asked that both the WHO and Congress ensure work on this topic differentiates explicitly between somatic cell gene editing and germline gene editing in oversight mechanisms. The Society will continue to be active in this evolving ethical and societal discussion.

CMS Decisions Cover but Reimburse Insufficiently for CAR T-Cell Therapy

In August 2019, the Centers for Medicare & Medicaid Services (CMS) released both its inpatient prospective payment system (IPPS) final rule for 2020 and finalized its decision memo on the CAR T-cell therapy national coverage analysis. In the IPPS final rule, CMS did take a positive step by increasing the new technology add-on payment (NTAP) cap from 50 percent to 65 percent for all new technologies. However, as stated in ASGCT comments to CMS [PDF 2], this NTAP cap could still leave hospitals that markup minimally with losses of over $300,000 per case. CMS’s final decision memo on the national coverage analysis for CAR T-cell therapy, however, contained most of ASGCT’s recommendations [PDF 3], including that CMS did not finalize its proposal for coverage with evidence development (CED). By instead issuing a national coverage determination (NCD) for CAR T-cell therapies, the additional administrative burden of a CED on providers is prevented, which could have resulted in patient access issues.

ASGCT Weighs in on ICER’s Value Assessment Changes

The Institute for Clinical and Economic Review (ICER), an organization that evaluates the clinical effectiveness and value of medical treatments, announced last month proposed changes to its methodology when evaluating “single or short-term transformative therapy.” ASGCT submitted comments to ICER last week, supporting the application of an adapted value assessment framework for these therapies, which can produce sustained major health gains or halt progression of significant illness.

Highlights of ASGCT recommendations include that ICER:

  • Add “scientific experts” to the list of stakeholders to consult to determine if a therapy qualifies for this category of treatment;
  • Treat uncertainty similarly to that for other treatments, with the exception that the one-time, or short-term, nature of these therapies warrants greater discussion of alternative payment models that allow for future risk sharing.
  • Consider additional elements of value, including the potential harms of delay of treatment of an effective therapy and the impact of treatments providing a novel mechanism of action on future innovation.

Because the research of ASGCT members for over two decades has culminated in the development of approved gene therapies, the Society will continue to advocate for fair and comprehensive determinations of their value to facilitate patient access to them.

Industry News

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