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Limbal Approach-Subretinal Injection of Viral Vectors for Gene Therapy in Mice Retinal Pigment Epithelium
Published on: August 7, 2015
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Retinal transduction profiles by high-capacity viral vectors
A Puppo1, G Cesi1, E Marrocco1
1Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy.
Gene Therapy
|July 4, 2014
Summary
Adeno-associated viral vectors are limited for inherited retinopathies due to large gene sizes. New viral vectors show potential for retinal gene therapy, but photoreceptor transduction remains a challenge.
Area of Science:
- Ophthalmology
- Gene Therapy
- Molecular Biology
Background:
- Adeno-associated viral (AAV) vectors are established for retinal gene therapy.
- AAV's limited cargo capacity restricts treatment for inherited retinopathies (IRs) caused by large genes (>5kb).
- Alternative viral vectors like adenovirus (Ad), lentivirus (LV), and herpes virus (HV) can carry larger payloads but show inefficient retinal photoreceptor (PR) targeting.
Purpose of the Study:
- To evaluate and compare the retinal transduction efficiency of various viral vectors beyond AAV.
- To identify Ad, LV, and HV vectors capable of targeting retinal photoreceptors for IR gene therapy.
- To assess the potential of these vectors for treating IRs linked to large gene mutations.
Main Methods:
- Systematic evaluation of mouse retinal transduction profiles.
- Testing of 16 Ad serotypes, 7 LV pseudotypes, and a bovine HV.
- Comparative analysis of photoreceptor (PR) and retinal pigment epithelium (RPE) transduction.
Main Results:
- Most tested vectors efficiently transduced the retinal pigment epithelium (RPE).
- Lentivirus-GP64 showed improved PR transduction compared to LV-VSVG, but in a limited region.
- Certain adenovirus vectors (HdAd1, 2, 5/F35++) demonstrated more extensive PR transduction than LV, though not surpassing AAV2/8.
Conclusions:
- Adenovirus vectors show promise for enhanced photoreceptor transduction in retinal gene therapy.
- Further optimization is needed to match AAV's broad PR transduction for treating inherited retinopathies.
- Exploring novel viral vector systems is crucial for overcoming AAV cargo limitations in gene therapy.
