Refining gene therapy for glaucoma using post-mortem human tissue

  • Research type

    Research Study

  • Full title

    Refining gene therapy for glaucoma using post-mortem human tissue

  • IRAS ID

    329242

  • Contact name

    Colin Chu

  • Contact email

    Colin.Chu@Bristol.ac.uk

  • Sponsor organisation

    Research and Enterprise Division, University of Bristol

  • Duration of Study in the UK

    3 years, 0 months, 0 days

  • Research summary

    Glaucoma is the leading cause of irreversible blindness worldwide. It is generally caused by chronically raised pressure in the eye that can damage the optic nerve and if left untreated, results in permanent vision loss.

    Current treatments include eye drops, laser treatment and surgery however there are limitations to all these treatment options. The ciliary body (CB) in the eye is the source of fluid production and the balance with how much enters and exits the eye affects the pressure.

    We are building on our research investigating the use of gene editing technologies such as CRISPR-Cas9. Aquaporin 1 (Aqp1) has been identified as a promising gene target in the ciliary body. Our research shows when injected in the mouse eye, CRISPR-Cas9 disruption of Aqp1 leads to a reduction of ocular pressure.

    A method of delivery is necessary to directly transport the treatments into the eye. Our transporter is a deactivated engineered virus called adeno-associated virus (AAV). Our group has been able to set up an in-house AAV manufacturing unit and are developing AAV to specifically target the ciliary body to be able to direct our therapy to Aqp1 genes in the ciliary body and not in other eye tissues would reduce off-target effects.

    We now need to use donor human eye tissues to test the different AAV and gene targets in the most appropriate way.

    In the future, an AAV gene therapy to target Aqp1 in the CB may provide an effective and long-lasting option to treat Glaucoma.

  • REC name

    HSC REC B

  • REC reference

    23/NI/0072

  • Date of REC Opinion

    16 May 2023

  • REC opinion

    Favourable Opinion