University finds falsified data in PNAS gene therapy paper, authors retract

A university investigation has found falsified data in a 2011 paper about the side effects of a virus commonly used in gene therapy.

The authors are retracting the paper, but one co-author told Retraction Watch they stand by their main conclusions. According to Roland Herzog, a professor at the University of Florida (UF) College of Medicine and a co-author of the paper, the falsified data were related to a minor part of the paper.

The paper, “Activation of the NF-κB pathway by adeno-associated virus (AAV) vectors and its implications in immune response and gene therapy,” was published in the Proceedings of the National Academy of Sciences (PNAS) in March 2011. All authors were affiliated with UF at the time; the handling editor, Kenneth Berns, is an emeritus professor at UF. The paper has been cited 50 times, according to Clarivate Analytics’ Web of Science.

According to the retraction notice, a UF Office of Research investigation looked into “concerns of duplication of panels in Figs. 3A and 6A.” The authors wrote in the notice:

The Committee found that although the images in Fig. 6A contained an inadvertent duplication, the results of this figure were subsequently verified independently. However, the Committee also found that the data presented in Fig. 3A were falsified. Unfortunately, no primary data files, experimental details, or records for the flow cytometry experiments in Fig. 3A could be produced.

PNAS told us UF informed them about the investigation in April 2016; it declined to say whether it considered issuing an editorial expression of concern in response. The paper has been cited eight times since the beginning of May 2016. 

Whether the investigation found a particular co-author responsible for the falsification remains unclear; UF has not yet replied to our request for comment.

Herzog told us that all authors agreed to the retraction. However, he said there was some “back and forth” with the journal about what to do:

…we have lost faith in those data in that particular figure, but it is not a main aspect of the paper…

It doesn’t affect any main conclusions. We believe they are still valid. Several other pieces have been independently verified in [the] sense they were repeated by different people. We know that the rest of the conclusions are valid. Now, what do you do in that kind of scenario? After back and forth, the senior author and the editors reached the conclusion it’s the cleaner thing to retract [the paper.]

To this point, the authors wrote in the notice:

While the precise role of the NF-κB pathway in primary human dendritic cells will require independent confirmation, none of the major conclusions reached in the paper is affected.

PNAS told us:

In October 2017, we learned that the institution had reached a conclusion, and we worked with the authors to finalize their retraction statement. Based on the outcome of the investigation, the authors agreed to retract the article in November 2017.

The journal added that even though the handling editor was also from UF, there was no conflict of interest as long as he hadn’t collaborated with the authors for at least 24 months.

Adeno-associated viruses (AAVs) are a well-characterized and popular vehicle for gene therapies. Earlier this week, the FDA approved the first AAV-based gene therapy, Luxturna, for inherited eye disease.

The 2011 PNAS paper examined one mechanism through which the virus caused an immune response, an unwanted side effect. Herzog told us that other researchers have shown that by blocking this mechanism, the response can be diminished. Based on this, he said:

I don’t think this retraction is really going to impact the field at all.

Herzog said that he could not comment on the UF misconduct investigation for “legal reasons;” he added that the corresponding author, UF professor Arun Srivastava, is traveling overseas.

Ashley Martino, one of three co-first authors of the paper and now a professor at St. John’s University in New York City, declined to discuss the retraction. The other two co-first authors — Giridhara Jayandharan, of India Institute of Technology Kanpur, and George Aslanidi, of the University of Minnesota and Mayo Clinic-affiliated Hormel Institute — have not yet replied to our request for comment.

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