Homology-Directed Repair (HDR) Services

Online Inquiry

Homology-Directed Repair (HDR) services represent a highly specialized and sophisticated approach within the field of gene editing, offering unparalleled precision in genetic modifications. This technique leverages the cell's natural DNA repair mechanisms to introduce specific changes at targeted sites within the genome, thereby facilitating the study of gene function, disease modeling, and the development of novel therapies. The significance of HDR cannot be overstated, as it allows for the correction of genetic defects with high fidelity, making it an invaluable tool in both research and clinical applications.

HDR occurs preferentially at a nick on the transcribed strand and is stimulated by transcription (D Allen, et al.,2023)

Overview Service Process Examples and Solutions Applications Frequently Asked Questions

Overview

Homology-Directed Repair (HDR) is a precise and efficient method for introducing targeted genetic changes using the cell's natural repair pathways. This technique typically involves the use of engineered nucleases, such as CRISPR/Cas9, TALENs, or zinc finger nucleases, to create double-strand breaks at specific locations in the DNA. A donor template, which carries the desired genetic modification flanked by homologous sequences to the target site, is then introduced. The cell utilizes this template to repair the break, thereby incorporating the new genetic information. This process allows for exact genetic corrections or the insertion of new genes, making HDR a powerful tool for precise genome engineering.

Service Process

The process of HDR involves a series of meticulous and interrelated steps:

Target Identification: Selecting the specific gene or genetic sequence to be edited based on the research objective or therapeutic goal. Accurate target identification is essential for the success of the HDR process.
Donor Template Design: Designing a donor template that carries the desired genetic modification flanked by sequences homologous to the target site. This template is critical for guiding the repair process.
Guide RNA Design: For CRISPR/Cas9, guide RNAs are designed to direct the nuclease to the precise DNA sequence, ensuring specificity and accuracy in creating the double-strand break.
Delivery of Components: Introducing the nuclease, guide RNA, and donor template into the target cells using methods such as electroporation, viral vectors, or lipid nanoparticles. Efficient delivery is vital for successful HDR.
Selection of Edited Cells: Isolating cells that have successfully undergone HDR. This selection process may involve the use of selectable markers or advanced sorting techniques to enrich the population of edited cells.
Validation: Confirming the presence and accuracy of the genetic modifications through sequencing and functional assays. This step ensures that the edits are precise and that the cells exhibit the expected phenotypic changes.

Examples and Solutions

The following table provides an overview of various case studies in HDR-based gene editing and the solutions we offer to support your research and therapeutic endeavors:

Case Study	Description	Solutions We Offer
Cystic Fibrosis Gene Correction	Correcting CFTR gene mutations in iPSCs to restore normal function.	CRISPR/Cas9 HDR, donor template design, validation assays, and differentiation protocols.
Duchenne Muscular Dystrophy Therapy	Inserting functional dystrophin gene into muscle stem cells.	TALENs/CRISPR/Cas9 HDR, donor template design, muscle cell differentiation, and preclinical testing.
Hemophilia Gene Therapy	Introducing functional F8 gene into hematopoietic stem cells.	CRISPR/Cas9 HDR, donor template design, cell therapy preparation, and clinical trial support.
Parkinson's Disease Research	Inserting mutations in neural stem cells to study disease mechanisms.	CRISPR/Cas9 HDR, donor template design, neural differentiation, and functional assays.
Beta-Thalassemia Correction	Correcting HBB gene mutations in hematopoietic stem cells.	CRISPR/Cas9 HDR, donor template design, cell therapy preparation, and validation assays.
Diabetes Research	Enhancing insulin production in pancreatic progenitor cells via gene insertion.	CRISPR/Cas9 HDR, donor template design, differentiation protocols, and functional testing.

Applications

The applications of HDR in gene editing are extensive and transformative, including:

Gene Correction: Precisely correcting mutations that cause genetic disorders, thereby restoring normal gene function.
Gene Insertion: Introducing new genes or regulatory elements to study their effects or develop novel therapies.
Disease Modeling: Creating accurate cellular models of diseases to investigate their underlying mechanisms and identify potential therapeutic targets.
Functional Genomics: Studying the roles of specific genes and regulatory elements in development, physiology, and disease.

Frequently Asked Questions

Q: What is Homology-Directed Repair (HDR)?

A: Homology-Directed Repair (HDR) is a gene editing technique that uses the cell's natural DNA repair mechanisms to introduce specific genetic changes. It involves creating double-strand breaks at targeted DNA sites and using a donor template to guide the repair, resulting in precise genetic modifications.

Q: How is HDR performed in gene editing?

A: HDR is performed using advanced nucleases like CRISPR/Cas9, TALENs, or zinc finger nucleases to create targeted double-strand breaks. A donor template with the desired modification is introduced, and the cell uses this template to repair the break, incorporating the new genetic information.

Q: What are the applications of HDR in gene editing?

A: Applications include gene correction to fix mutations causing genetic disorders, gene insertion to study gene function or develop therapies, disease modeling to create accurate cellular models, and functional genomics to investigate gene roles and regulatory elements.

Q: What are the key steps in the HDR process?

A: Key steps include target identification, donor template design, guide RNA design (for CRISPR/Cas9), delivery of editing components into cells, selection of successfully edited cells, and validation of genetic modifications through sequencing and functional assays.

Q: Why is HDR important in gene editing?

A: HDR is important because it allows for precise and specific genetic modifications, enabling the correction of genetic defects, the study of gene function, the modeling of diseases, and the development of novel gene therapies.

For more information about our Homology-Directed Repair (HDR) Services or to discuss your specific needs, please contact us. Our team of experts is available to provide guidance and support for your research projects, ensuring you achieve your scientific and therapeutic goals.

Please note that all services are for research use only. Not intended for any clinical use.

Get a free quote

If your question is not addressed through these resources, you can fill out the online form below and we will answer your question as soon as possible.