With several recent gene therapy approvals in space and more on the horizon, the field of rare genetic diseases is experiencing a transformative era. The field of rare genetic kidney diseases, including ADPKD remains no exception to this, with gene therapy emerging as a promising alternative to treat this chronic kidney condition.  

At InnoSer, our ADPKD platform supports the testing of multiple therapeutic approaches, including small molecules, antibody-based therapeutics, and various gene therapy approaches. The most straightforward approach to test the efficacy of a putative gene therapy approach in our ADPKD mouse model is the direct injection of viral vectors containing the gene of interest via the i.v. route.  

However, injecting viral vectors (most commonly using adeno-associated virus [AAV]) via the i.v. route requires systematic injection of high viral vector doses in order to reach the kidney. This approach therefore may pose some disadvantages and risks, among which are off-target effects, as well as cost and scaling disadvantages, especially when one considers the clinical applicability.  

Therefore, for drug developers using gene therapy as a therapeutic strategy for ADPKD treatment, InnoSer can advise on efficacy studies of gene therapy via local kidney injection using specialized surgical techniques (Figure 1).  

FIGURE 1. Surgical methods for targeted kidney gene therapy delivery. Surgical approaches to test novel gene therapy approaches include i) renal artery injection ii) venous injection iii) transparenchymal renal pelvis injection iv) hydrodynamic renal pelvis injection and v) intraparenchymal injection.

Injecting gene therapy via the different direct routes has been shown to transduce different types of cells (with different efficacy levels) within the kidney, leading to exogenous gene expression in different segments of the kidney (Khare et al., 2024). For this reason, optimization experiments are recommended to determine which surgical technique is the most appropriate for your targeted gene delivery. InnoSer’s team will work together with you to optimize the best gene delivery surgical technique for your approach, whilst taking into account the mechanism of action (MoA) of your therapy. 

InnoSer’s ADPKD mouse model platform offers three different mouse models (P10, P18 & P40), each resulting in different disease model due to the different timings of Pkd1 knockout. Therefore, depending on which mouse model is used, gene therapy can be used as a therapeutic treatment in the P18 mouse model but both as a prophylactic and therapeutic treatment in the P40 mouse model.  

Reach out to our team to obtain expert guidance on best model selection, including tailored study designs and to collaborate with expert ADPKD study leads and biotechnicians to help you obtain high-quality data.  

Are you exploring innovative delivery strategies for gene therapies in CNS diseases? InnoSer has extensive experience in optimizing gene therapy delivery for multiple CNS disorders, utilizing advanced approaches like intrathecal, ICV, and stereotactic injections to achieve targeted delivery. These methods are designed to overcome challenges such as BBB penetration and off-target effects, ensuring precision and efficacy in preclinical research. 

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