BRAIN Initiative: Production and distribution facilities for brain cell type-specific access reagents (U24 Clinical Trial Not Allowed)

BRAIN Initiative: Production and distribution facilities for brain cell type-specific access reagents (U24 Clinical Trial Not Allowed) is sponsored by National Institutes of Health (NIH) Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative. This BRAIN Initiative Notice of Funding Opportunity (NOFO) aims to support the establishment of facilities at minority-serving institutions (MSIs) and Institutional Development Award (IDeA)-eligible institutions for scaled production and distribution of brain cell type-specific …

RFA-MH-25-105: BRAIN Initiative: Production and distribution facilities for brain cell type-specific access reagents (U24 Clinical Trial Not Allowed) This funding opportunity was updated to align with agency priorities. Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations National Institute of Mental Health ( NIMH ) National Eye Institute ( NEI ) National Institute on Alcohol Abuse and Alcoholism ( NIAAA ) National Institute of Biomedical Imaging and Bioengineering ( NIBIB ) Eunice Kennedy Shriver National Institute of Child Health and Human Development ( NICHD ) National Institute on Deafness and Other Communication Disorders ( NIDCD ) National Institute on Drug Abuse ( NIDA ) National Institute of Neurological Disorders and National Center for Complementary and Integrative Health ( NCCIH ) Funding Opportunity Title BRAIN Initiative: Production and distribution facilities for brain cell type-specific access reagents (U24 Clinical Trial Not Allowed) U24 Resource-Related Research Projects – Cooperative Agreements March 31, 2025 - This funding opportunity was updated to align with agency priorities.

Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. April 04, 2024 - Overview of Grant Application and Review Changes for Due Dates on or after January 25, 2025. See Notice NOT-OD-24-084 August 31, 2022 - Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023.

See Notice NOT-OD-22-198 . August 5, 2022 - Implementation Details for the NIH Data Management and Sharing Policy. See Notice NOT-OD-22-189 .

Funding Opportunity Number (FON) Companion Funding Opportunity Research Project (Cooperative Agreements) See Section III. 3. Additional Information on Eligibility .

Assistance Listing Number(s) 93. 242, 93. 865, 93.

853, 93. 286, 93. 866, 93.

213, 93. 173, 93. 273, 93.

279, 93. 867 Funding Opportunity Purpose This Notice of Funding Opportunity (NOFO) from the NIH Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative is intended to support dissemination facilities for scaled-up production and distribution of a specific set of brain cell type-specific access reagents to study circuit function.

Production and Distribution Facilities will be supported to disseminate hundreds of reagents specifically from Reagent Resource for Design and Development projects developed under RFA-MH-25-100 . This NOFO will support facilities to interface with these specific reagent development projects, scale up reagent production, disseminate reagents broadly, and coordinate reagent data distribution.

The types of reagents to be produced and distributed could include but are not limited to viral vectors, nucleic acid constructs, and nanoparticles designed for selective access to hundreds of brain cell types. Such reagents will enable neuroscientists to probe circuit function with high precision in experimental animals and ex vivo human tissue and cells.

Facilities are needed to contribute to the production and distribution of reagents broadly to neuroscience researchers. This NOFO is part of the BRAIN Initiative Armamentarium project, whose overall goal is to generate tools to specifically access, manipulate, and monitor brain cell types across multiple vertebrate species.

This NOFO will foster close interaction between technologists, disseminators, and neurobiologists in a research consortium including investigators funded by other Armamentarium NOFOs.

Open Date (Earliest Submission Date) Letter of Intent Due Date(s) 30 days prior to the application due date(s) Renewal / Resubmission / Revision (as allowed) AIDS - New/Renewal/Resubmission/Revision, as allowed All applications are due by 5:00 PM local time of applicant organization.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

Required Application Instructions It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide , except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts ). Conformance to all requirements (both in the Application Guide and the NOFO) is required and strictly enforced.

Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

There are several options available to submit your application through Grants. gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

Use the NIH ASSIST system to prepare, submit and track your application online. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants. gov and eRA Commons to track your application.

Check with your institutional officials regarding availability. Workspace to prepare and submit your application and eRA Commons to track your application. Part 1.

Overview Information Part 2. Full Text of Announcement Section I. Notice of Funding Opportunity Description Section II.

Award Information Section III. Eligibility Information Section IV. Application and Submission Information Section V.

Application Review Information Section VI. Award Administration Information Section VII. Agency Contacts Section VIII.

Other Information Part 2. Full Text of Announcement Section I.

Notice of Funding Opportunity Description Since 2014, the Brain Research through Advancing Innovative Neurotechnologies® (BRAIN) Initiative has aimed to accelerate the development and application of innovative neurotechnologies, enabling researchers to produce a new dynamic picture of the brain that reveals how individual cells and complex neural circuits interact in both time and space.

It is expected that these advances will ultimately lead to new ways to treat and prevent brain disorders. The NIH encourages businesses to participate in the BRAIN Initiative. It is possible for companies to submit applications directly to BRAIN Initiative program announcements or to collaborate with academic researchers in joint submissions.

Small businesses should consider applying to one of the BRAIN Initiative small business NOFOs. The BRAIN Initiative requires a high level of coordination and sharing between investigators. It is expected that BRAIN Initiative recipients will cooperate and coordinate their activities after awards are made by participating in Program Director/Principal Investigator (PD/PI) meetings and in other activities such as the annual PI meeting.

The data sharing expectations for BRAIN Initiative awards can be found at NOT-MH-19-010 . This NOFO is related to the transformative project, "A Cell Type-Specific Armamentarium for Understanding Brain Function and Dysfunction," described in the " The BRAIN Initiative 2. 0: From Cells to Circuits, Toward Cures " report of the Advisory Committee to the NIH Director BRAIN Initiative Working Group 2.

0. Scaled Production and Distribution Facilities for Brain Cell-Type Specific Access Reagents Recent progress in experimental neuroscience has been driven by new methods and technologies. These have in turn inspired new discoveries and hypotheses.

Among new technologies are reagents to access and manipulate specific brain cell types in experimental animals and human ex vivo tissue and cells (e.g., adeno-associated viral (AAV) vectors, lentiviral (LV) vectors, rabies viral vectors, nanoparticles, improved transgenic engineering methods, molecular sensors of neural activity, optogenetic and chemogenetic effector proteins, gene editors).

These molecular and genetic tools enable the dissection of neural circuit function through the precise delivery of mapping, monitoring, and manipulation reagents. Novel reagents have enabled the detailed study of neural activity with sub-second timing and across thousands of individual neurons in behaving animals. A dynamic and detailed picture of the brain in relation to behaviors has started to emerge.

Increasing numbers of brain cell types are being defined based on comprehensive transcriptomic, epigenomic, and anatomical profiling. Significant progress has been made in defining this diversity through a census of mammalian brain cell types, supported by the BRAIN Initiative Cell Census program.

The BRAIN Initiative Cell Census effort was initiated in 2014 to define a brain parts list with unprecedented detail through molecular and anatomical profiling of the mouse, non-human primate, and human brain. By 2023, the program together with other efforts succeeded, for example, in defining nearly 5000 cell types in the mouse brain with transcriptomic and anatomical position information.

Many more brain cell types have been and will continue to be delineated in other mammalian species including humans. The BRAIN Initiative Armamentarium project intends to leverage this brain cell type information to create molecular or genetic access reagents to deliver mapping, monitoring, and manipulation payloads to distinct circuit components.

The intention is for the breadth of Armamentarium project reagents to transform the dissection of neural circuits underlying behavior by experimental neuroscientists. The Armamentarium project is conceptually aimed at enabling unique access to each molecularly defined brain neural cell type that could exhibit a distinct cellular, circuit, or behavioral function.

The BRAIN Initiative Armamentarium project began with 8 awards made in 2021-2023 under RFA-MH-20-556 and RFA-MH-21-180 . These initial awards formed the Armamentarium Consortium. The initial goal of the consortium was to evaluate scalable molecular genetic technologies, production, and distribution for cell type-selective reagents across several vertebrate species.

Scalable technologies were established by pilot projects in several areas, including: improved gene regulatory element discovery, engineering of more selective viral vector tropism, multiplexed screening for specific enhancers and minimally invasive viruses in various species, novel RNA editing-based and microRNA control strategies, and higher throughput in situ hybridization validation methods.

Based on this progress, the Armamentarium project is supporting further scale up of cell type-selective access by Reagent Resources for Design and Development (RRDDs) through RFA-MH-25-100. This NOFO is intended to support scaled Production and Distribution Facilities (PDFs) to disseminate the reagents specifically from the RRDDs to neuroscience researchers.

Widespread deployment of these scaled reagents is a critical step for facilitating functional circuit dissection. Many different cell types will become genetically accessible with the new reagents. This is particularly important for understanding circuits in less genetically tractable species, like non-human primates.

Augmenting the scale of production and distribution is needed to disseminate the Armamentarium reagents to experimental neuroscience researchers.

The purpose of this NOFO is to support PDFs to scale up production and distribution of hundreds of brain cell type-selective access reagents for several vertebrate species, including human ex vivo tissue and cells, developed specifically by Armamentarium RRDD projects for use by neuroscience researchers. PDFs supported by this NOFO must execute 4 main functions.

First, the PDFs must interface specifically with the Armamentarium RRDD project investigators (recipients of RFA-MH-25-100 ), who will design, validate, and catalogue brain cell type-selective access reagents for several vertebrate species, including ex vivo human tissue and cells.

RRDD projects will also adapt the reagents into easily disseminable formats (e.g., DNA proviral constructs for viruses) that can be readily transferred to PDFs for distribution to neuroscience researchers. Second, the facilities must conduct scaled-up production of the RRDD designed and validated reagents. Third, the facilities must disseminate RRDD reagents to neuroscience research users.

Fourth, to aid reagent dissemination through distribution of reagent characterization data, the facilities must coordinate RRDD reagent data and metadata distribution to BRAIN Initiative data archives and other archives, neuroscience researchers, and the Armamentarium Consortium members. Specific goals for areas 1-4 are: 1. Interfacing with Armamentarium RRDDs Each facility must work with at least one Armamentarium RRDD.

In terms of this interface between PDFs and RRDDs, the goal of this NOFO is to support PDFs that: Receive all validated reagent designs, reagent templates, and/or seed reagents from the RRDD partner(s) that were made under RFA-MH-25-100 . Improve the reagents, optimize the scaling up of reagent production, and/or further catalogue the reagents.

Produce reagents that could include but are not limited to viral vectors, nucleic acid constructs, and nanoparticles designed for selective access to and manipulation of brain cell types. The reagent types for production will depend on the nature and progress of the RRDD projects.

NIH will facilitate additional collaborations with the RFA-MH-25-100 recipients to coordinate production and distribution of reagent types as appropriate through a research consortium (see further below). 2. Scaled-up Reagent Production Each facility must scale up production of all the validated reagents from one or more RRDDs.

In terms of this scaling up of reagent production, this NOFO is intended to support PDFs that: Scale up reagent production for hundreds of reagents and a variety of reagent unit quantities for use in several vertebrate species, including mice, non-human primates, and human ex vivo tissue and cells. Incorporate robust quality control for reagents and quality assurance for production processes.

Characterize, formulate, evaluate, and validate the efficacy, reproducibility, stability, activity, and unique characteristics of the produced reagents. Ensure purified reagents are safe and appropriate for use in animals and/or human ex vivo tissue and cells. Manufacture reagents for the minimal inventory for distribution.

Neuroscience research users requesting reagents will pay for future production costs. 3. Disseminating Reagents to Neuroscience Researchers Each facility must disseminate the scaled-up product inventory to neuroscience research users as broadly as possible.

In terms of this dissemination, the goal of this NOFO is to support PDFs that: Make and maintain reagent catalogues that are widely accessible. Deliver reagents to users. Assess the ongoing user demand for various reagents as well as to receive and incorporate constructive user feedback.

User feedback could include information on reagent performance, quality, quantity, timeliness, ordering processes, delivery, cost, feature requests, and related issues. Create a website to achieve the above user interface objectives. Conduct reagent storage, inventory management, and domestic and international distribution activities.

The management and oversight of distribution activities could include, but are not limited to, material transfer and licensing agreements, webhosting, and recovery of production and distribution costs. Include project management efforts for distribution of hundreds of validated reagents from one or more RRDDs at the facility. Recover reagent shipping costs paid by neuroscience research requestors.

4. Reagent Data Coordination Facilities must coordinate RRDD reagent data and metadata distribution to BRAIN Initiative data archives and other archives, neuroscience researchers, and the Armamentarium Consortium members.

Overall, Armamentarium reagent data are distributed at 4 venues: (A) BRAIN Initiative data archives (mainly for secondary analysis of these data by others), (B) PDF reagent catalogues where neuroscience research users can obtain reagents, (C) catalogues/atlases with detailed reagent expression data created at the RRDDs, and (D) meetings that include the Armamentarium Steering Group meetings for Armamentarium Consortium members.

In terms of the reagent data coordination, the goal of this NOFO is to support PDFs that: Ensure that all RRDD project data and metadata for reagent engineering and validation are deposited in a timely manner at (A) according to the BRAIN Initiative Data Sharing Policy . Ensure that accessible interfaces are maintained to link (B) to (C). Ensure that accessible interfaces are maintained to link (B) to (A).

Organize (D) to facilitate communication within the consortium about reagent data. Working Together in the Armamentarium Consortium Supported projects are expected to work closely together and benefit from membership in the Armamentarium Consortium of researchers, including other Armamentarium recipients from this NOFO, RFA-MH-20-556 , RFA-MH-21-180 , RFA-MH-22-245 , and RFA-MH-25-100.

Coordination among consortium members is expected to include sharing of technologies, reagents, and data to improve brain cell type-selective access reagents, as well as cooperation in publication and reagent distribution to integrate the best technologies into neuroscience research.

This consortium is expected to include tool developers and disseminators funded by several Armamentarium efforts for brain cell access reagent engineering, reagent production and distribution, and optimization of high-impact reagents for monitoring and manipulating brain cell activity.

The consortium will hold regular meetings (in-person and via videoconference) and conduct other coordinated activities within the consortium as well as in the BRAIN Initiative more broadly. Because this NOFO supports scaled PDFs, it is expected that facilities will have scaled up production and distribution goals. Applications must include proposed milestones and a proposed timeline.

Final versions of each will be agreed upon at the time of award. The proposed milestones and timeline should explain critical indicators of progress for the interfacing with RRDDs, scaled-up reagent production, disseminating reagents, and reagent data coordination. The final agreed upon and approved milestones will be specified in the Notice of Award.

If justified, future year milestones may be revised based on data and information obtained in the current year. Examples of responsive research activities include, but are not limited to: 1. Interfacing with Armamentarium RRDD projects: Receiving all the validated reagent designs, templates, and/or seed reagents from one or more Armamentarium RRDDs made under RFA-MH-25-100.

Transfer of large collections of DNA plasmids encoding proviral or transgenic sequences for cell type-selective access reagents. Receiving reagent production protocols, cell lines, and/or other unique materials needed for manufacturing. Feedback to RRDD projects on produced viral particle titer levels to help improve reagent designs to facilitate large-scale production and use.

Communication with RRDD projects to harmonize reagent nomenclature with the catalogue made available to neuroscience researchers to obtain reagents. 2. Scaled-up Armamentarium RRDD Reagent Production.

Validated reagents from Armamentarium RRDD projects to be produced at high scale could include: Adeno-associated viral (AAV) or lentiviral (LV) vectors containing transcriptional regulatory elements that enable selective or specific expression of neural activity monitoring or manipulation payloads in molecularly defined brain cell types that could have functional relevance.

Reagents related to scalable use of somatic cell, CRISPR gene editing to knock in monitoring or manipulation constructs to a collection of gene loci that contain cis regulatory elements that drive expression in specific brain cell types. AAV capsid variants to selectively transduce brain neural cell types.

Lipid nanoparticles containing surface proteins that mediate selective transduction of brain neural cell types with genetic constructs. LV vectors pseudotyped with antibody or nanobody proteins to mediate selective transduction of brain neural cell types targeting cell surface antigens.

Transgenic mouse, rat, zebrafish, or other vertebrate responder lines containing widely used reporter, monitoring, or manipulation constructs that can be combined with molecular access driver reagents to be expressed in specific brain neural cell types.

Transgenic or genome engineered animals having knock in reporter, monitoring, or manipulation constructs passed through the germline and targeted to gene loci for brain cell type-specific expression that are produced in a manner that very substantially reduces the time, cost, and breeding required by current methods in experimental vertebrate organisms.

Combinations of molecular access reagents that intersectionally refine expression or delivery of monitoring and manipulation constructs to brain cell types with greater specificity. Collection of systemically administered viral or non-viral reagents that efficiently cross the blood brain barrier and direct construct expression to molecularly defined brain cell types and that detarget peripheral organs.

Viral or non-viral vectors that enable neuronal projection mapping of or transsynaptic tracing initiated from defined brain cell types. RNA-based reagents to target brain cell types based on nucleic acid complementarity, protein-RNA interaction, or other interactions. 3.

Disseminating Armamentarium RRDD Reagents to Neuroscience Researchers: Widespread dissemination of cell type access and manipulation reagents for brains of vertebrate animals and/or human ex vivo brain tissue or cells to identify, characterize, and/or alter potentially disease-relevant neural cells or circuits.

Creation and maintenance of website-based catalogues of produced access reagents for users, showing inventory levels, efficacy, reproducibility, stability, activity, and unique characteristics of reagents; providing data on ongoing demand; and enabling receipt and incorporation of constructive user feedback on reagent performance, quality, quantity, timeliness, ordering processes, delivery, cost, feature requests, and related issues.

Broad distribution of reagent use protocols that define parameters and methods for brain cell type-selective reagent use administered systemically or intracranially to minimize undesirable, perturbative effects of vectors or payloads.

Large-scale brain cell type-selective reagent manufacturing and dissemination platforms that ensure quality control, quality assurance, and adequate supply for neuroscience community users, including assessment of the quality of reagents. Integration of data on reagent performance, improvement of reagents, and provision of feedback to reagent designers.

Organization of reagent inventories and management of domestic and international deliveries to users. 4. Armamentarium Reagent Data Coordination: Tracking RRDD project reagent data and metadata deposition at BRAIN Initiative data archives.

Creating website links for reagents in PDF catalogues, where neuroscience research users can order reagents, to the additional reagent data catalogued at the RRDD projects. Creating website links in PDF reagent catalogues to reagent data at BRAIN Initiative data archives.

Organizing in-person and/or videoconference meetings that include the Armamentarium Steering Group meetings to facilitate communication within the consortium about reagent data.

Non-responsive Areas of Research The following research areas are considered outside the scope of this NOFO, and such applications will be considered non-responsive and will not be reviewed: Applications that fail to propose to address all four main functions of a PDF: (1) interfacing with one or more RRDDs, (2) scaled-up RRDD validation reagent production, (3) disseminating reagents, and (4) Armamentarium reagent data coordination.

Applications that fail to include proposed milestones and a proposed timeline. Applications primarily focused on the pursuit of a biological mechanism or a hypothesis through basic research that does not result in the generation of a scaled-up reagent production and distribution facility. Studies primarily focused on technology development that do not propose a scalable reagent resource.

Note: Applications for technology development may be submitted to a separate BRAIN Initiative NOFO (including RFA-MH-24-280 , RFA-MH-23-295 , or reissues). See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information Cooperative Agreement: A financial assistance mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities.

See Section VI. 2 for additional information about the substantial involvement for this NOFO. Application Types Allowed The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

Only those application types listed here are allowed for this NOFO. Not Allowed: Only accepting applications that do not propose clinical trials. Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards Issuing IC and partner components intend to commit an estimated total of $2,400,000 per year to fund 2 to 4 awards. Application budgets are not limited but need to reflect the actual needs of the proposed project. The maximum project period is 5 years.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO. Section III. Eligibility Information All organizations administering an eligible parent award may apply for a supplement under this NOFO.

Higher Education Institutions Public/State Controlled Institutions of Higher Education Private Institutions of Higher Education Nonprofits Other Than Institutions of Higher Education Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education) Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education) For-Profit Organizations (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Recognized) Eligible Agencies of the Federal Government - Including the NIH Intramural Program U.S. Territory or Possession Independent School Districts Public Housing Authorities/Indian Housing Authorities Native American Tribal Organizations (other than Federally recognized tribal governments) Faith-based or Community-based Organizations Non-domestic (non-U.S.) Entities (Foreign Organizations) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply. Foreign components, as defined in the NIH Grants Policy Statement , are allowed. Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award.

All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference NIH Grants Policy Statement Section 2.

3. 9. 2 Electronically Submitted Applications for additional information.

System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually . The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.

NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM. Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM. gov registration process.

The same UEI must be used for all registrations, as well as on the grant application. eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants. gov registration; all registrations must be in place by time of submission.

eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application. Grants. gov – Applicants must have an active SAM registration in order to complete the Grants.

gov registration. Program Directors/Principal Investigators (PD(s)/PI(s)) All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons.

If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal Investigator) Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide. This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1. 2 Definition of Terms .

3. Additional Information on Eligibility Applicant organizations may submit more than one application, provided that each application is scientifically distinct. The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.

3. 7. 4 Submission of Resubmission Application .

This means that the NIH will not accept: A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application. A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.

An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2. 3. 9.

4 Similar, Essentially Identical, or Identical Applications ). Section IV. Application and Submission Information 1.

Requesting an Application Package The application forms package specific to this opportunity must be accessed through ASSIST, Grants. gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.

gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution. 2.

Content and Form of Application Submission It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced.

Applications that are out of compliance with these instructions may be delayed or not accepted for review. Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review. By the date listed in Part 1.

Overview Information , prospective applicants are asked to submit a letter of intent that includes the following information: Descriptive title of proposed activity Name(s), address(es), and telephone number(s) of the PD(s)/PI(s) Names of other key personnel Participating institution(s) Number and title of this funding opportunity The letter of intent should be sent to: All page limitations described in the How to Apply – Application Guide and the Table of Page Limits must be followed.

Instructions for Application Submission The following section supplements the instructions found in the How to Apply – Application Guide and should be used for preparing an application to this NOFO. All instructions in the SF424 (R&R) Application Guide must be followed. SF424(R&R) Project/Performance Site Locations All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Other Project Information All instructions in the SF424 (R&R) Application Guide must be followed. SF424(R&R) Senior/Key Person Profile All instructions in the SF424 (R&R) Application Guide must be followed. Applicants may include project management personnel for the proposed facilities for the production and distribution of reagents as Senior/Key Person(s).

All instructions in the SF424 (R&R) Application Guide must be followed. Include the following costs in each annual budget: Costs for product development, characterization, and testing to maintain a minimal inventory of reagents. Costs should include the purification, formulation, vialing, characterization, evaluation, quality control, quality assurance and/or other related activities.

Costs for project management and website/catalogue development and maintenance. Costs for attendance at the anticipated annual in-person meeting for the research consortium. Do not include in the budget: Production costs to manufacture reagents beyond the minimal inventory for distribution.

Neuroscience research users requesting reagents are required to pay for production costs. Shipment and delivery of reagents. Neuroscience research users requesting reagents are required to pay for shipping costs.

All instructions in the SF424 (R&R) Application Guide must be followed. PHS 398 Cover Page Supplement All instructions in the SF424 (R&R) Application Guide must be followed. All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions: Throughout the Research Strategy, applicants must address a Production and Distribution Facility plan as outlined below.

Significance: For each Specific Aim individually or for all Specific Aims collectively, explain the following: How the project will align with the overarching goal of the BRAIN Initiative Armamentarium project to generate molecular or genetic reagents to specifically access brain cell types in the study of circuit