With several recent gene therapy approvals in the CNS space and more on the horizon, the field of both genetic and neurodegenerative diseases is experiencing a transformative era. However, translating these therapies from preclinical research to clinical application remains challenging.   

At InnoSer, we specialize in helping you optimize gene therapies tailored to your therapeutic modality (e.g., RNA-based therapeutics, ASOs, CRISPR-Cas9), delivery systems (e.g., AAV-vectors, lentiviral or adeno-associated viral vectors, non-viral nanoparticles such as LNPs), administration routes (IV, ICV, intrathecal), as well as experience in medical devices to enhance BBB penetration and region-specific delivery. 

InnoSer’s expert biotechnicians ensure precise injections with minimal variance (> 90% correct injections) and maximized reliability. InnoSer’s experts are specialized in the following administration routes: 

• IV: Conventional IV injections (e.g., tail vein) are routinely performed at InnoSer, representing one of the most straightforward approaches for gene therapies that cross the blood-brain barrier. Retro-orbital injections into the venous sinus are routinely performed as well.  

• ICV: Intracerebroventricular (ICV) injections enable widespread delivery across the rodent brain. Routinely performed studies at InnoSer involve single ICV injections in neonatal pups and/or adult mice. Multiple repeated ICV injections can be performed via chronic cannula implantation. Chronic infusion can be performed via osmotic minipumps.  

• Intrathecal delivery: bypasses the BBB minimizing systemic exposure and potential off-target effects. 

• Intraspinal delivery: Administer compounds directly to spinal cord regions. 

• Intracerebral delivery into different brain regions: depending on target brain region, InnoSer can perform stereotactic surgery injections to locally deliver compounds, making this approach particularly relevant for therapies requiring localized brain-region targeting.  

• Chronic cannulation into cisterna magna (ICM): chronic cannulation studies into cisterna magna are possible at InnoSer in rats.  

InnoSer provides on-site breeding and advanced models of monogenetic diseases (Fragile X Syndrome, Epileptic Encephalopathy Stxbp1) and multiple CNS diseases like Alzheimer’s disease and Parkinson’s disease. Our team can conduct proof-of-concept and optimization studies to help you: 

• Assess transduction/transfection efficiency (qPCR, Western blotting, IHC) 

• Evaluate downstream disease-related phenotypes after gene manipulation 

• Investigate off-target effects and delivery specificity to CNS cells 

• Optimize strategies between different administration routes (e.g., IV vs ICV) and dosages (single and/or repeated dosing; dosing possible from PND1 for in-house animal colonies) 

• Assess immunogenicity and immune response 

• Determine biodistribution e.g., via IVIS bioluminescence (working with vectors with luciferase-tagged reporter genes)  

• Evaluate the use of advanced techniques (such as medical devices) for transient BBB opening, BBB bypassing, and region-specific delivery 

In a representative experiment, InnoSer evaluated the efficiency of CRISPR/Cas9-mediated gene editing using Ai9 mice (Figure 1). 

FIGURE 1. Gene editing efficacy optimizing experiment example. The efficiency of CRISPR/Cas9-mediated gene editing can be evaluated by using strains such as Ai9. Ai9 mice express robust tdTomato fluorescence following Cre-mediated recombination. Thus, the Ai9 strain enables the quantification of fluorescent signal in the targeted muscle tissue following intramuscular injection of iTOP® CRISPR/Cas9 targeted to remove the STOP codon (A), which normally prevents the expression of tdTomato. Following CRISPR/Cas9-mediated recombination (B), the skeletal muscle of the Ai9 strain transcribe the tdTomato gene. The representative image (red: tdTomato) (C) underscores the efficiency of CRISPR/Cas9-mediated gene editing following optimization studies. Complementary gene and protein expression analysis with longitudinal in vivo luminescent imaging follow-up in turn provide highly relevant insight in biodistribution and gene editing efficiency. 

Are you exploring other innovative delivery strategies for gene therapies for rare (non-CNS) genetic diseases? InnoSer has extensive experience in gene therapy delivery for other rare genetic disease mouse models, such as ADPKD, where direct gene delivery to the kidney is one of the leading therapeutic strategies. Read more about the commonly employed methods of direct gene delivery to kidneys here.

Ready to elevate your preclinical research? Let’s work together to ensure your gene therapy achieves optimal clinical outcomes.