COVID-19, small RNAs, and conflicts of interest

Recently a paper published in Nucleic Acid Therapeutics, a Mary Liebert publication not to be confused with the more glamorous Nucleic Acid Research journal, was brought to my attention. It described the potential use of small RNAs as a therapeutic against SARS-CoV-2.

Alas, it is most memorable because of the alarmingly short time-to-acceptance, lack of references, and the omission of several conflicts of interest.

The paper in question is the following:

Oligonucleotides and the COVID-19 Pandemic: A Perspective – John J Rossi and Daniel Rossi – Nucleic Acid Therapeutics (2020), DOI: 10.1089/nat.2020.0868. Published online April 13, 2020.

Most of the text in this blog post is identical to my concerns that I posted today on PubPeer.

In this paper, Rossi and Rossi describe several oligonucleotide-based approaches as options to combat SARS-CoV-2, such as siRNA, antisense oligos, or aptamers. Such small RNA or DNA oligonucleotides could be uses as therapeutics because they might bind to specific regions in the viral genome, and thus maybe prevent it from replicating or infecting new host cells.

Unfortunately, there are several concerns about this paper that should have been caught during peer review.

Not giving credit

Although the paper describes several other studies done on SARS-CoV-2, there are no references to that work. Science builds on science, as I have written before, meaning that scientists almost always build upon the work done by others before them. It is professional to credit the previous work by others by including those papers in the References section of a scientific paper.

This paper only has 2 citations, which belong to the papers from which they have copied the illustrations from (with permission). None of the other work that is mentioned in this paper is listed in the citations.

For example, the authors mention drug research studies, genomic sequencing of the SARS-CoV-2 virus, phylogeny of the virus, how the virus binds to host cells, etc. All that work was done by other groups, and it is custom and professional in scientific papers to credit the work by others by listing those papers in the citations. Why did the authors not credit the work by so many others?

Hidden Conflicts of Interest

Secondly, there appears to be some missing conflicts of interest. There is an “Author Disclosure Statement”, which mentions that DR is the interim president of iSTAT Therapeutics.

The other author, JJR, lists an affiliation with the Beckman Research Institute of City of Hope, in Duarte, CA, United States. According to Wikipedia, this is a private non-profit:

Screenshot from the discussed paper, DOI: 10.1089/nat.2020.0868, showing the disclosed conflict of interest of the second author, 2 citations, and affiliation of the first/corresponding author.

What appears to be missing from the Author Disclosure Statement is that one of the authors, JJR, is the (co-)founder of several companies in the field of small oligonucleotides. He is the co-founder of Dicerna Inc and Calando Pharmaceuticals, both companies that use oligonucleotide molecules (e.g. RNAi) as therapeutics. In addition, Dr. JJ Rossi is listed as the co-founder of MiNA Therapeutics. He also holds several granted patents and patent applications that appear to involve small RNA-based oligonucleotides, including a patent on Dicer Substrate siRNA.

These are all great accomplishments, but it is a bit unfortunate that none of these potential conflicts of interest made it to the Author Disclosure Statement. It seems likely that not only DR, as disclosed, but also JJR might financially benefit from this paper.

Fast Peer Review

Also, as visible from the screenshot above, the paper was received, peer reviewed, revised, and accepted within 3 days. It was submitted on Friday April 3, and accepted on Tuesday April 7, suggesting that most of this editorial and review work was done in the weekend.

One would have hoped that e.g. the lack of citations and potential conflicts of interests would have been noticed by e.g. an editor or peer reviewer.

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