Cellectis Presents Novel TALEN Editing Processes Enabling Highly Efficient Gene Correction and Gene Insertion in HSPCs - Seite 2

This novel editing approach is an important addition to the HSPC gene editing toolbox that might unlock new strategies for the treatment of metabolic and neurological diseases. 

Research data showed that:

• Intron editing can be performed within B-cell, T-cell, Monocyte-specific endogenous genes (CD20, CD4 and CD11b, respectively)
  
  
• Intron editing allows expression of transgenes in a lineage-specific manner without markedly impacting the expression of the endogenous gene targeted
  
  
• Editing of CD11b intron using a therapeutic transgene encoding IDUA (the enzyme missing in Type-1 Mucopolysaccharidosis patients) enables to restrict the expression of IDUA to the myeloid lineage.
  
  
• Edited HSPCs efficiently engraft in the bone-marrow of immunodeficient mice and differentiate into edited myeloid cells that can cross the BBB and populate the brain.
  
  
• The intron editing strategy described in this work is versatile and could be potentially used to vectorize multiple genetically encoded-therapeutic proteins to the brain and thus address multiple metabolic and neurological disorders.
  
  

Title: Intron Editing of HSPC Enables Lineage-Specific Expression of Therapeutics 

Presenter: Julien Valton, Ph.D., Vice President Gene Therapy at Cellectis 
Session Date/Time: May 5, 2024 at 12PM ET  
Session Title: Gene Targeting and Gene Correction New Technologies 
Presentation Room: Exhibit Hall 
Final Abstract Number: 721  

Poster presentation: Circularization of Non-Viral Single-Strand DNA Template for Gene Correction and Gene Insertion Improves Editing Outcomes in HSPCs 

Today, most of the gene insertion approaches used to edit HSPCs ex vivo are hampered by the low efficiency of DNA template delivery into their nucleus.

Cellectis has developed and optimized a novel gene editing process, leveraging the TALEN technology and circular single strand DNA template delivery, enabling highly efficient gene insertion in HSPCs. 

Research data showed that:

• Non-viral single strand DNA delivery associated to TALEN technology allows gene insertion in long-term repopulating hematopoietic stem cells
• Circularization of the single strand DNA further increases the rates of gene insertion without impacting cellular viability and fitness of HSPCs, facilitating the development of next generation of ex vivo cell therapies

Title: Circularization of Non-Viral Single-Strand DNA Template for Gene Correction and Gene Insertion Improves Editing Outcomes in HSPCs