Journal of Genetic Syndromes & Gene Therapy
Open Access

Applications of Adeno Associated Virus Vectors in Treating Hemophilia and Retinal Diseases

Krister Boettcher^{* *}Correspondence: Krister Boettcher, Department of Child and Adolescent Psychiatry, University Medical Center Hamburg, Eppendorf, Germany, Email:

Author info »

Description

Adeno Associated Virus (AAV) vectors are a type of viral vector that have gained significant attention in gene therapy study due to their unique properties and effectiveness in delivering therapeutic genes to human cells [1]. AAV is a non-disease-causing, single-stranded Deoxyribonucleic acid (DNA) virus that is classified under the parvoviridae family [2]. Despite being a virus, AAV does not cause disease in humans and has been found to be remarkably safe, making it an ideal candidate for gene delivery. AAV vectors are engineered to carry genetic material into target cells, where they can integrate or remain episomal in the cell, enabling long-term expression of the desired therapeutic genes [3].

AAV vectors have several advantages that make them particularly useful in gene therapy applications. First, AAVs are relatively small in size, which allows them to carry a therapeutic gene, along with necessary regulatory elements, into cells effectively. Additionally, AAVs have a low immunogenic profile, meaning they are less likely to trigger an immune response compared to other viral vectors. This characteristic is important for ensuring the long-term success of gene therapy, as repeated treatments may be required without eliciting a strong immune response that could limit the effectiveness of the therapy [4].

Another important characteristic of AAV vectors is their capacity to target a diverse range of tissues and organs. This versatility is a result of the various serotypes of AAV that exist, each with its own preference for specific cell types [5]. Analysts can select the appropriate AAV serotype based on the tissue or organ that needs to be targeted, allowing for more precise delivery of the therapeutic gene. For example, certain AAV serotypes are particularly effective at targeting muscle cells, while others are better suited for targeting liver cells or neurons. This adaptability makes AAV vectors an attractive option for treating a wide range of genetic diseases [6].

AAV vectors are used in gene therapy to treat a variety of genetic disorders, particularly those caused by a single defective gene [7]. Examples include hemophilia, muscular dystrophy and retinal degenerative diseases. For instance, in the case of hemophilia B, a condition caused by a deficiency in the clotting factor IX, AAV vectors can be used to deliver a functional copy of the factor IX gene to the liver, where it is produced and secreted into the bloodstream, helping to restore normal blood clotting. Similarly, AAV-based gene therapy has been used to treat certain inherited retinal diseases, such as Leber congenital amaurosis and retinitis pigmentosa, by delivering genes that produce the necessary proteins for vision to retinal cells [8].

In addition to their application in inherited genetic diseases, AAV vectors are also being examined for the treatment of cancer, neurodegenerative diseases and other conditions. In cancer therapy, for example, AAV vectors can be engineered to deliver genes that either enhance the immune response against cancer cells or directly target and kill cancerous cells [9]. For neurodegenerative diseases like Parkinson's disease, AAV vectors can deliver genes that produce neuroprotective factors or replace defective genes involved in the disease process, offering potential long-term therapeutic benefits.

Despite the promising potential of AAV vectors, there are still challenges that need to be addressed. One of the key challenges is the limited capacity of AAV vectors to carry large therapeutic genes. AAV vectors can typically accommodate only genes that are relatively small, which may limit their use for certain diseases that require the delivery of larger genes. Analysts are working on developing new strategies, such as engineered AAV vectors and split-gene approaches, to overcome this limitation and enable the delivery of larger genetic payloads.

Another challenge is the potential for immune responses against AAV vectors. Although AAV vectors are generally less immunogenic than other viral vectors, some individuals may have pre-existing antibodies against certain AAV serotypes due to prior exposure to the virus [10]. This can hinder the effectiveness of gene therapy, as the immune system may recognize and neutralize the vectors before they can deliver the therapeutic gene. To address this, analysts are exploring strategies to minimize immune responses, such as using less common AAV serotypes or modifying the vector to evade immune detection. Additionally, long-term efficacy is still an important question in AAV-based gene therapies. While AAV vectors are known to provide long-lasting gene expression in many cases, there is variability in the duration of expression, depending on factors such as the target tissue.

Conclusion

In AAV vectors represent a powerful tool in the field of gene therapy, offering a safe and effective method for delivering therapeutic genes to treat a variety of genetic disorders. Their ability to target different tissues, low immunogenicity and long-term gene expression make them an attractive option for many applications. While challenges remain in terms of gene size limitations, immune responses and long-term efficacy, ongoing study and advancements in vector engineering continue to improve the potential of AAV-based therapies. As the field progresses, AAV vectors could play an important role in the development of new treatments for genetic diseases, cancer and other challenging conditions.

References

1. Bhunia S, Kolishetti N, Vashist A, Yndart Arias A, Brooks D, Nair M. Drug delivery to the brain: recent advances and unmet challenges. Pharmaceutics. 2023;15(12):2658.

   [Crossref] [Google Scholar] [PubMed]

2. Hagen S, Baumann T, Wagner HJ, Morath V, Kaufmann B, Fischer A, et al. Modular adeno-associated virus (rAAV) vectors used for cellular virus-directed enzyme prodrug therapy. Sci Rep. 2014;4(1):3759.

   [Crossref] [Google Scholar] [PubMed]

3. Allen D, Knop O, Itkowitz B, Kalter N, Rosenberg M, Iancu O, et al. CRISPR-Cas9 engineering of the RAG2 locus via complete coding sequence replacement for therapeutic applications. Nat Commun. 2023;14(1):6771.

   [Crossref] [Google Scholar] [PubMed]

4. Kucharzik T, Ellul P, Greuter T, Rahier JF, Verstockt B, Abreu C, et al. ECCO guidelines on the prevention, diagnosis and management of infections in inflammatory bowel disease. J Crohns Colitis. 2021;15(6):879-913.

   [Crossref] [Google Scholar] [PubMed]

5. Hotta A. Genome editing gene therapy for Duchenne muscular dystrophy. J Neuromuscul Dis. 2015;2(4):343-355.

   [Crossref] [Google Scholar] [PubMed]

6. Haseltine WA, Hazel K, Patarca R. RNA Structure: Past, Future and Gene Therapy Applications. Int J Mol Sci. 2024;26(1):110.

   [Crossref] [Google Scholar]

7. Dinculescu A, Link BA, Saperstein DA. Retinal gene therapy for Usher syndrome: current developments, challenges and perspectives. Int Ophthalmol Clin. 2021;61(4):109-124.

   [Crossref] [Google Scholar] [PubMed]

8. Keeler AM, Flotte TR. Recombinant adeno-associated virus gene therapy in light of Luxturna (and Zolgensma and Glybera): where are we and how did we get here?. Annu Rev Virol. 2019;6(1):601-621.

   [Crossref] [Google Scholar] [PubMed]

9. Lee CS, Bishop ES, Zhang R, Yu X, Farina EM, Yan S, et al. Adenovirus-mediated gene delivery: potential applications for gene and cell-based therapies in the new era of personalized medicine. Genes Dis. 2017;4(2):43-63.

   [Crossref] [Google Scholar] [PubMed]

10. Machhi J, Shahjin F, Das S, Patel M, Abdelmoaty MM, Cohen JD, et al. Nanocarrier vaccines for SARS-CoV-2. Adv Drug Deliv Rev. 2021;171:215-239.

    [Crossref] [Google Scholar] [PubMed]