*MICHEL MEUNIER

Novel Non-Invasive Laser-Assisted Intraocular Drug Delivery System for an Efficient and Selective Gene Transfer Therapy

Challenge: Retinal degenerative diseases, such as age-related macular degeneration and glaucoma, are the leading causes of vision loss and affect tens of millions of individuals in the world. Emerging solutions with nucleic acids and therapeutic genes show promise. However, there remains a void in effective and non-invasive drug delivery systems for the back of the eye, which has hindered the development of effective treatment modalities for retinal degenerative diseases. A safe, precise and highly efficient drug delivery system targeting difficult-to reach retinal layers would open novel therapeutic avenues.

Solution: The proposed research program aims to develop a non-viral ocular gene delivery system for retinal ganglion cells (RGCs) and retinal pigment epithelium (RPE) cells using ultrafast lasers amplified by gold nanoparticles. This new delivery system is based on near-infrared ultrafast laser irradiation, which is not absorbed by biological tissues, and as such is not harmful to the eye. In addition, the method offers the advantages of high selectivity and efficiency as well as excellent reproducibility at low toxicity.

Achievements/Impact: The team has developed a process to obtain stable gold nanoparticles with biopolymers and antibodies, in order to selectively target retinal cells in the presence of serum proteins. These functionalised gold nanoparticles concentrate the laser energy thereby allowing perforation of the cell membrane and gene delivery into targeted cells. The technique was developed with three types of ultrafast lasers and was successfully validated in vitro with human retinal cell culture, with ex-vivo explants as well as in vivo within rodent eyes. Using this new method, the team showed effective small interfering RNA (siRNA) delivery in living cells and further demonstrated the absence of toxicity both in vitro and in vivo.
Nanoparticle-assisted laser technology has the potential to enable novel therapeutic and research avenues by providing a powerful tool for delivery of therapeutic biomolecules to the back of the eye.

Principal Investigator:

Michel Meunier
Polytechnique Montréal

Co-investigators

Mike Sepieha
Université de Montréal

Santiago Costantino
Université de Montréal

Completed Project
$473,000 / 2 years
Supported by CQDM through:
• AstraZeneca
• Merck
• Pfizer
• Boehringer Ingelheim
• GSK
• Eli Lilly
• Novartis
• MESI
• BL-NCE
And by co-funding partner:
• CHRP