75N95020Q00265_SOW.pdf

Version 11-30-2016-1 FAR Part 11—Describing Agency Needs

STATEMENT OF WORK

GENERAL INFORMATION

Title of Project:

iNDI-Plus (iNDI+), additional alleles for the iPSC NeuroDegeneration Initiative project

Statement of Need and Purpose:

To generate a collection of up to 414 engineered isogenic Alzheimer's disease and related dementias (ADRD)-mutation iPSC lines. This is the fundamental starting point for the INDI intiative.

Background Information and Objective:

Contractor to provide genetically engineered iPSCs for the purpose of creating a national cell repository as an open resource for the scientific community and as a tool to characterize how mutations change fundamental biological properties of disease-relevant cell types.

Period of Performance:

Base period of performance from September 1, 2020- August 31, 2021 plus (2) options years September 1, 2020-August 31, 2022 September 1, 2022-August 31, 2023

SCOPE OF WORK

General Requirements:

Independently and not as an agent of the Government, the Contractor shall furnish all the necessary services, qualified personnel, material, equipment, and facilities, not otherwise provided by the Government as needed to perform the Statement of Work below.

Specific Requirements:

Contractor will generate a collection of up to 414 engineered isogenic Alzheimer's disease and related dementias (ADRD)-mutation iPSC lines. The allele type, number of projects/genes and number of independent clones will be as follows:

1) Revertant alleles of iNDI SNV alleles, 130 projects, 3 or more independent clones

2) Homozygous knockouts, up to 77 genes, 2 or more independent clones

3) HaloTag alleles, up to 77 genes, 2 or more independent clones

4) HaloTag in SNV allele, up to 130 projects, 2 or more independent clones

Each line will harbor one of the four allele types in either wild-type iPS cells or a selected SNV-containing clone, as specified by Government. Contractor will recover 3 or more independent revertant clones for each of the 130 SNV projects. Contractor will endeavor to generate at least 2 independent clones of the other three allele types (knockout and HaloTag alleles), however, if fewer than 2 clones are proven to be isolated, recovery experiments should not be continued.

Platforms used by vendor must include:

Delivery of Cas9–sgRNA ribonucleoprotein (RNP)to facilitate editing human iPSCs.

Demonstration of high efficiency CRISPR/Cas9-mediated editing of knockin and deletion alleles would be more relevant for this project

Generation of knockout alleles should be performed by one of two strategies. The first strategy is the deletion of most or all of the protein coding exons of the target gene. The second approach introduces a premature stop codon in the body of the gene by HDR.

Generation of N- or C-terminal HaloTag alleles will be performed separately in wild-type and in SNV-containing cells using plasmid donors provided by the Government.

Molecular confirmation must be provided to show that the SNV allele is tagged.

LEVEL OF EFFORT:

Vendor staff will provide the assay results via reporting transfer thru email.

GOVERNMENT RESPONSIBILITIES

The government will provide iPSC starting material to vendor.

DELIVERY OR DELIVERABLES

For each engineered iPSC project, two or more independent clones will be expanded and archived in quadruplicate 96-well Matrix™ storage plates each containing 8 vials per clone. We will be sending two of the quadruplicate 96-well Matrix plates (i.e., two copies of the resource) to the NIH or to NIH-designated repositories. The contractor will keep the other two copies for long-term storage and distribution to researchers upon request.

REPORTING REQUIREMENTS

The vendor is to provide documentation regarding:

a. General method of engineering employed for each line, including information about the nuclease used and protein/plasmid based delivery (e.g. WT spCas9 RNP, TALENs, plasmid-based CRISPR, etc)

b. Karyotyping results for 390 edited cell lines Whole genome sequencing of 390 samples, including genomic DNA extraction.

OTHER CONSIDERATIONS

Travel:

The principal place of performance is the vendor’s work site. Travel for contractor employees will not be necessary.

Key Personnel:

Vendor will provide a dedicated project manager to the government as a point of contact for the services.

Information System Security Plan:

Not Applicable

Data Rights:

Section 508—Electronic and Information Technology Standards:

The contractor shall comply with Section 508 of the Rehabilitation Act (29 U.S.C. § 794d), as amended by the Workforce Investment Act of 1998 (P.L. 105-220), August 7, 1998.

Publications and Publicity:

Confidentiality of Information: