Gene Therapy Development for Cystic Fibrosis

Cystic fibrosis (CF) is a recessively inherited disease resulting from mutations in the cystic fibrosis trans-membrane conductance regulator (CFTR) gene. Over the last twenty-five years or more, gene therapy has been developed as a novel treatment for CF. Additionally, the therapeutic gene editing for CF treatment is rapidly developing with the emergence of the CRISPR/Cas9 technology and chemically modified mRNA therapeutics. Creative Biolabs is a world-renowned service provider for cystic fibrosis gene therapy and offers the one-stop, full custom services including the viral and non-viral gene therapy, small RNA and Gene editing for CF, etc. In a word, we are aiming to accelerate our client's gene therapeutic development.

Figure 1. Therapeutic strategies for gene therapy of cystic fibrosis (Hart 2017)

Featured Services for Cystic Fibrosis Gene Therapy Strategies

• Viral Gene Therapy

The viral gene therapy categories become a natural initial choice due to the assumed innate capability of viruses to infect the respiratory tract. Current gene therapy studies for CF using engineered adenovirus (Ad) or adeno-associated Virus (AAV) focus on approaches to reducing immunogenicity, expanding the tropism of vectors, and enhancing CFTR expression levels and persistence in the lung. Lentivirus is another attractive vector for CF gene therapy because of their ability to produce long-term, stable gene expression by integrating into the recipient genome. In addition, packaging of full length CFTR and strong promoters is not size-limited as with AAV, which shows promising potential for their use in CF gene therapy.

• Non-viral Gene Therapy

The non-viral categories are usually lipid-based, but also include nanoparticles. Clinical trails performed with gene liposome formulation have demonstrated the safety, ease of scalable formulation and packaging capacity of lipid-based vector. Another interesting, alternative, non-viral approach to CF gene therapy takes advantage of biodegradable poly polymers and exosomes. Some groups have shown that the exosomes from CFTR-expressing epithelial cells are incubated with CFTR-mutated CF15 cell line and found to restore CFTR protein production and ion transport functionality to CF15 cells.

• Gene Editing for CF

Gene editing is a novel option for CF therapy performed by repairing the specific mutations in CFTR or disrupting coding sequences in contributory genes and cryptic splice sites in CFTR, such as the approaches of CRISPR/Cas9, transcription activator-like effector nucleases (TALENs), all of which acting on the mutation site and repaired by endogenous DNA repair pathways or Homology Directed Repair (HDR) or Non-Homologous End-Joining (NHEJ).

Figure 2. Genome Editing Technologies Exploit Endogenous DNA Repair Machinery (Hsu 2014)

With the spirit of non-stop exploration, Creative Biolabs has generated an all-round platform to provide the gene therapy development service for CF treatment. Well-trained and experienced technicians perform all our experiments and we are confident to help you to make an ideal research plan according to your targets and downstream applications. Please feel free to contact us and we will not let you down.

Reference

1. Hart, S. and Harrison, P. (2017). Genetic therapies for cystic fibrosis lung disease. Current Opinion in Pharmacology, 34, pp.119-124.
2. Hsu, P., Lander, E. and Zhang, F. (2014). Development and Applications of CRISPR-Cas9 for Genome Engineering. Cell, 157(6), pp.1262-1278.
3. Cooney, A., McCray, P. and Sinn, P. (2018). Cystic Fibrosis Gene Therapy: Looking Back, Looking Forward. Genes, 9(11), p.538.