Reading Room Production — page 16

164-06 (received date ated 2ring for investigators in this field are to create cDNA I know UNC-Chapel Hill you know where this was he From: "Stemmy, Erik (NIH/NIAID) [E]" </O=EXCHANGELABS/OU=EXCHANGE ADMINISTRATIVE GROUP (FYDIBOHF23SPDLT)/CN=RECIPIENTS/CN=585133D3FA194F06AA618678B2817C22STEMMYEJ> To: "Sanders, Ashley (NIH/OD) [E]" < @nih.gov>, "Linde, Emily (NIH/NIAID) [E]" < @mail.nih.gov> Cc: "Shannon, Mike (NIH/OD) [E]" < @nih.gov> Subject: RE: Grant Questions - FBI Inquiry - 1-R01AI110964-01 - 2-R01AI110964-06 Date: Thu, 21 May 2020 17:49:51 -0400 Importance: Normal Attachments: SF_424_AI110964.docx Hi Ashley, Since we'll only have a short time on Tuesday I thought it might be helpful to provide the agent my responses to the original questions. There may be some misunderstanding of gain-of-function experiments, so hopefully this will clarify some things or at least provide a framework for our discussion next week. Thanks! Erik p.s. I've also pasted the response directly below in case there is an issue adding an attachment to an encrypted message. SF 424 AI110964-06 (received date 11/05/2018) Both SF 424s seem to be describing "gain of function" experiments. On page 192 of SF 424 AI110964-06 (received date 11/05/2018) under P3CO Research, it indicates they are conducting gain of function of SARSr-CoV. The funding pause on gain-of-function (GoF) experiments was in place from 2014-2017, and explicitly involved work reasonably anticipated to enhance the transmissibility or pathogenicity of influenza, MERS-CoV, or SARS-CoV. As such, that policy would not have applied to SARS-related coronaviruses (SARSr-CoV). The replacement policy, Potential Pandemic Pathogen Care and Oversight (P3CO), requires additional review and oversight of experiments that are anticipated to increase a potential pandemic pathogen's transmissibility or pathogenicity in humans. The viruses created under this award are chimeric bat viruses, which generally would not be anticipated to cause enhanced disease or transmission in people. When evaluating experiments for potential GoF or P3CO we determine the likelihood of altering one of these attributes compared to the wild-type or circulating viral strain. Were they also conducting Seemless Cloining and Assembly? From a review of their experimental details, it looks as if they were generating recombinant DNA of the viruses using WIV1 as the backbone but I could not determine if they were using Seemless Cloning techniques. I'm not aware of them using seamless cloning. Standard techniques for investigators in this field are to create cDNA molecular clones, which are then expressed in cull culture. I could not determine exactly where they were conducting these gain of function experiments. I know UNC-Chapel Hill has done these but within the document, I could not determine where this was occurring. Do you know where this was occurring? GoF experiments were not conducted as part of this award. While chimeric viruses were created via this award, they would not be considered GoF since the results did not confer attributes that were not already exhibited by the wild type versions of the viruses. For example, expressing the spike protein of SARS-CoV in the WIV-1 backbone did not increase the