Novel Gene Therapy Approach Delivers Large Genes

A breakthrough by University of Zurich (UZH) researchers introduces a versatile technique for efficiently and safely delivering substantial genes, holding significant promise for therapeutic applications.

Novel Gene Therapy Approach Delivers Large Genes
The new method REVeRT (reconstitution via mRNA trans-splicing) is more efficient and flexible in application. Image Credit: istock.com/DrAfter123.

While gene therapy stands as the most encouraging avenue for treating genetic disorders, it encounters several obstacles that limit its broader implementation. One such challenge involves the effective delivery of genetic material into target cells while minimizing any adverse effects. This task often relies on adeno-associated viral vectors (AAVs).

AAV carrier substances offer a favorable combination of safety and effective gene transfer efficiency, making them a common choice in gene therapies and CRISPR/Cas gene editing. However, AAVs face a constraint in their ability to carry larger genes consistently.

Historically, numerous approaches have emerged to overcome this limitation. These methods involve dividing the coding DNA into two fragments capable of recombination within the target tissue. However, these strategies suffer from inefficiency, limited flexibility in experimental design, and the risk of potential side effects.

Assembly at Transcript Leve

Professor Elvir Becirovic and his team, specializing in experimental and translational ophthalmology at the University of Zurich, have introduced an innovative solution to address these limitations.

Their novel approach, named REVeRT (reconstitution via mRNA trans-splicing), utilizes the dual AAV vector concept. However, unlike prior methods, it hinges on the reassembly of fragmented gene segments at the transcript level.

The advantages of this method are increased efficiency and fewer side effects. It is also more flexible than previous methods, as the large genes can be divided into two fragments at various points.”

Elvir Becirovic, Professor, Experimental and Translational Opthalmology, University of Zurich

Furthermore, his team has adapted this method for ophthalmological applications in cell cultures and conducted successful assessments in diverse animal models, including its application for the treatment of hereditary macular degeneration through gene therapy.

Possible Therapies for Various Diseases

REVeRT exhibits versatility for deployment in gene therapies addressing a spectrum of genetic or acquired disorders, encompassing prevalent blood conditions and age-related diseases.

Additionally, this innovative approach holds promise for integration into gene therapy investigations involving CRISPR/Cas genome editing. In the context of these therapeutic interventions, the seamless transfer of coding DNA into target cells is essential for maximum efficiency, often relying on carriers like AAVs.

With CRISPR/Cas further applications are possible, opening up new treatment options.”

Elvir Becirovic, Professor, Experimental and Translational Opthalmology, University of Zurich

Source:
Journal reference:

Riedmayr, L. M., et al. (2023) mRNA trans-splicing dual AAV vectors for (epi)genome editing and gene therapy. Nature Communications. doi.org/10.1038/s41467-023-42386-0.

Comments

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of AZoLifeSciences.
Post a new comment
Post

While we only use edited and approved content for Azthena answers, it may on occasions provide incorrect responses. Please confirm any data provided with the related suppliers or authors. We do not provide medical advice, if you search for medical information you must always consult a medical professional before acting on any information provided.

Your questions, but not your email details will be shared with OpenAI and retained for 30 days in accordance with their privacy principles.

Please do not ask questions that use sensitive or confidential information.

Read the full Terms & Conditions.

You might also like...
Scientists Pinpoint Gene Linked to Neuronal Susceptibility in Alzheimer’s Disease