IDT Debuts Protein Solution to Improve CRISPR Knock-In Accuracy

In an effort to enhance efficient homology-directed repair (HDR)—HDR being one of the most persistent bottlenecks in clustered regularly interspaced short palindromic repeats (CRISPR) gene editing—Integrated DNA Technologies (IDT) has launched a new protein-based solution, Alt-R HDR Enhancer Protein. Based on the company’s Sept. 25, 2025 announcement, this solution has been shown to increase HDR efficiency by as much as two-fold in challenging cell types, such as induced pluripotent stem cells and hematopoietic stem and progenitor cells (1).

The ability to achieve more precise genome modifications without compromising cell health or genomic integrity is central to advancing cell and gene therapy pipelines. While CRISPR-Cas systems have proven highly effective at generating gene knockouts through non-homologous end joining, knock-in strategies via HDR have remained considerably less efficient, particularly in primary and difficult-to-edit cells (2). This imbalance has constrained the pace of translational research and delayed movement toward scalable therapeutic applications.

“IDT’s legacy of innovation … and strong collaborations with gene editing pioneers enabled us to develop a first-to-market Alt-R HDR Enhancer Protein that delivers on … therapeutic research needs and [a] desire to fast-track breakthroughs,” said Sandy Ottensmann, vice-president and general manager, Gene Writing & Editing, IDT, in a company press release (1). “It’s exciting to see from early access users that this pathway-specific protein-based enhancer shifts the DNA repair pathway balance toward HDR, promoting more precise genome modification without compromising cell viability or genomic integrity, demonstrating its scalability in therapeutic development applications.”

What does the introduction of this new protein-based solution mean for next-gen therapy manufacturing?

Various studies using the Alt-R HDR Enhancer Protein demonstrated a consistent increase in HDR activity across different loci and cell types, the company stated in its press release. Importantly, the protein does not appear to introduce off-target edits or chromosomal translocations, addressing a key concern in the development of therapeutic-grade cell products. This finding suggests that protein-based HDR enhancers could be a reliable component of high-fidelity editing workflows, supporting applications ranging from basic research through translational studies (1).

The new enhancer represents an additional tool for biomanufacturers that can be used to standardize editing performance in development workflows. The solution is designed to be compatible with multiple Cas systems and widely used delivery methods, making it easier for laboratories and process development teams to integrate the enhancer into existing pipelines without disrupting established practices, according to IDT. The product is initially available in research-use-only format, with a clinical-grade manufacturing version to follow, which the company said reflects the growing demand for reagents that bridge discovery-stage research and current good manufacturing practice environments.

How does this new tool position next-gen therapeutics?

By expanding the currently available toolkit for precise editing, IDT is reinforcing the link between technological innovation and clinical translation in CRISPR-based therapeutics. The enhancer protein is manufactured by US-based Aldevron, a Danaher company, under strict quality standards, underscoring the importance of aligning reagent development with the needs of clinical manufacturing (1).

As developers of cell and gene therapies increasingly require solutions that maintain editing accuracy while ensuring scalability, the introduction of protein-based enhancers such as Alt-R HDR has the potential to improve manufacturing reliability and accelerate the translation of genome engineering strategies into clinical practice. With challenges around HDR efficiency representing a major hurdle in advancing CRISPR from research to therapeutic application, this new launch offers a practical step forward for the cell and gene therapy community.

References

1. Integrated DNA Technologies. Integrated DNA Technologies Launches New Enhancer Protein to Accelerate CRISPR-based Therapies from Translational Research to Clinical Breakthrough. Press Release. Sept. 25, 2025.
2. Liao, H.; Wu, J.; VanDusen, N. J.; et al. CRISPR-Cas9-Mediated Homology-Directed Repair for Precise Gene Editing. Mol. Ther.—Nucleic Acids 2024, 35 (4), 102344. DOI: 10.1016/j.omtn.2024.102344