# Improving The Reproducibility and Genetic Stability of IPSC and Differentiated Cells Through Oncogene-Free Reprogramming and Fully Human Growth Factors

> **NIH NIH R44** · CELLULAR ENGINEERING TECHNOLOGIES, INC · 2021 · $346,021

## Abstract

Cellular Engineering Technologies (CET) has submitted this proposal in response to RFA-GM-
19-001. CET has proposed a direct Phase II SBIR application to create more reproducible
human induced pluripotent stem cells (iPSCs) and create methods for growing, maintaining,
and authenticating iPSCs. A major challenge in iPSC manufacturing and subsequent
differentiation is the emergence of genetic instability that result from non-random chromosomal
mutations. Genetic instability results in clonal expansion of genetic variants that increases
iPSC heterogeneity. The experimental variables that promote genetic instability are not well
understood. Yet, oncogene-dependent reprogramming and prolong cell culturing are clearly
linked to genetic instability. Moreover, prior iPSC reprogramming methods adapted for
preclinical research have not been optimized to mitigate against the infectious, inflammatory,
neoplastic and genetic risks for cell therapy. Thus, iPSC reprogramming should be
standardized to include non-integrating, virus-free and oncogene-free methods, which would
offer reproducible iPSC in adherent and suspension cells. This milestone would mitigate
oncogenic and viral effects that could reduce genetic instability in iPSC manufacturing and
differentiation. Further, iPSC reproducibility and differentiation would improve if growth factors
displayed fully human posttranslational modification (PTM). While bacterial-manufactured
growth factors and non-human glycosylated peptides and proteins are ubiquitous in the stem
cell field, they exhibit differential bioactivity than their native human counterparts. Thus, using
growth factors that lack a fully human PTM may amplify the genetic instability and distort cell
phenotype of iPSC and differentiated cells, particularly for multiple differentiation steps that
require multiple growth factors. CET is a biotechnology company with a diverse pipeline of
human somatic stem cells and a first-in-class non-integrating, feeder-free, virus-free and
oncogene-free iPSC reprogramming approach that has been validated and published for
adherent cells and suspension cells. Moreover, CET is the sole source manufacturer of select
postnatal stem cells. These capabilities allowed CET to obtain immortalized human postnatal
stem cells designed for biologic bioprocessing of fully human PTM. Thus, CET is poised to
develop iPSC and differentiated cells through manufacturing processes that mitigate genetic
instability. The focus of this proposal will be to develop a manufacturing platform to create GLP
and GMP-grade iPSC with the least amount of genetic instability even after subsequent
neuroprogenitor cell differentiation.

## Key facts

- **NIH application ID:** 10239237
- **Project number:** 5R44GM139403-02
- **Recipient organization:** CELLULAR ENGINEERING TECHNOLOGIES, INC
- **Principal Investigator:** Alan B Moy
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $346,021
- **Award type:** 5
- **Project period:** 2020-08-15 → 2022-08-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10239237

## Citation

> US National Institutes of Health, RePORTER application 10239237, Improving The Reproducibility and Genetic Stability of IPSC and Differentiated Cells Through Oncogene-Free Reprogramming and Fully Human Growth Factors (5R44GM139403-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10239237. Licensed CC0.

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