Adenovirus vectors and adeno-associated viruses are non-integrated vector techniques, which means that DNA with the correct CFTR gene is inserted into an individual’s cells, but the DNA does not become a part of the cell’s genome. 4 The disadvantage of this technique is that it is not permanent.
Full Answer
Is gene therapy for cystic fibrosis closer to reality?
While the implementation of a cystic fibrosis gene therapy technique has been more challenging than previously expected, new research continues to bring the vector systems closer to reality. Keywords: cystic fibrosis, gene therapy, viral vectors, non-viral vectors, CFTR gene
Do lentiviral vectors have a role in CF gene therapy?
While lentiviral vectors have not been tested in CF clinical trials, they have a sufficient packaging capacity for a CFTR expression cassette and can transduce non-dividing cells [ 21, 22 ]. This is particularly important for CF gene therapy because most airway epithelial cells are mitotically quiescent [ 23, 24 ].
How is cystic fibrosis (CF) corrected in vitro?
Correction of the cystic fibrosis defect in vitro by retrovirus-mediated gene transfer. Cell. 1990; 62 :1227–1233. [ PubMed] [ Google Scholar] [ Ref list]
Can LV vectors transduce the airway epithelium in cystic fibrosis mice?
Lentiviral (LV) vectors, of the Retroviridae family, show interesting properties for CF gene therapy, since they integrate into the host genome and allow long-lasting gene expression. Proof-of-principle that LV vectors can transduce the airway epithelium and correct the basic electrophysiological defect in CF mice has been given.
What vector should be used for cystic fibrosis?
Since the cystic fibrosis gene was discovered in 1989, researchers have worked to develop a gene therapy as an ultimate cure. One of the most promising and enduring vectors is the adeno-associated virus (AAV), which has been shown to be safe in several clinical trials.
Does somatic therapy use viral vectors?
Abstract. Recombinant adenoviral vectors are one of the most common vectors used for somatic gene therapy secondary to their high-production titer and their high-gene transfer efficiency to a variety of tissues.
Which gene therapy is best for cystic fibrosis?
Trikafta works for people with cystic fibrosis who have at least one copy of the F508del mutation in their CFTR genes. That accounts for around 90% of those with the condition.
Why is adeno-associated virus the best vector for cystic fibrosis?
Recombinant adeno-associated virus (rAAV) has attracted increasing attention as a vector for gene therapy of CF because it naturally infects the airway epithelial cells and has not been associated with any disease. Vectors derived from AAV can infect nondividing cells and provide prolonged gene expression.
What are hybrid vectors?
Viral hybrid vectors are defined as vectors which combine the high transduction rates of viruses with genetic elements for stable maintenance of therapeutic DNA. This article focuses on recombinant viral hybrid vectors with the ability to integrate their therapeutic DNA into the host genome of eukaryotic cells.
How do you choose a vector for gene therapy?
In conclusion, there are many kinds of vectors available for gene therapy, each with their own advantages and disadvantages. Which one to choose for your project comes down to factors like the size of the transgene, the kind of gene therapy target cells used, how the transgene should be expressed and more.
How is CF treated with gene therapy?
The treatment uses a type of virus called a lentivirus to deliver a healthy copy of a gene called CFTR, which causes cystic fibrosis when it carries a mutation. The gene therapy will be given by inhalation to better target the right cells.
Why is ex vivo gene therapy better?
The advantage of ex vivo gene therapy is the ability to characterize the genetically modified cells extensively and select them for desired phenotypes before using them for therapy. The property of the cells may also be chosen to enhance the therapeutic potential.
What gene is affected by cystic fibrosis?
Summary. Cystic fibrosis is caused by mutations in the gene that produces the cystic fibrosis transmembrane conductance regulator (CFTR) protein. In people with CF, mutations in the CFTR gene can disrupt the normal production or functioning of the CFTR protein found in the cells of the lungs and other parts of the body ...
Can Crispr cure cystic fibrosis?
Curing genetic diseases Now that the researchers showed that the mutations that cause CF can be safely corrected, applications in the clinic come one step closer. "New variants of CRISPR/Cas9, such as prime editing, can safely correct mutations without causing damage in other regions of the DNA.
What is AAV gene therapy?
AAV vectors are bioengineered tools that use a non-enveloped virus to transport modified genetic material safely into tissues and cells impacted by otherwise difficult-to-treat conditions.
What are the challenges of gene therapy?
RisksUnwanted immune system reaction. Your body's immune system may see the newly introduced viruses as intruders and attack them. ... Targeting the wrong cells. ... Infection caused by the virus. ... Possibility of causing a tumor.
What are non-viral vectors?
Non-viral vectors are made from synthetically produced biological molecules. 16 In addition, the rapid progress of nanotechnology has enabled the gene delivery of these nanosized particles. Typically, with nanoparticle delivery systems, the plasmid DNA which carries the gene expression cassette is bound to a synthetic chemical compound that is then released at the delivery site. 16 Early studies have shown that non-viral vectors can transfer the functional CFTR gene to the CF airway epithelia in vivo and partially correct the anion transport defect. 17 Carriers generally contain cationic lipids or cationic polymers because they bind with high affinity to the negatively charged DNA. 18 In terms of gene transduction, non-viral vectors are less efficient, but their availability, cost, and low immunogenicity make them a possible long-term solution.
What is lentivirus vector?
The lentivirus vectors are a promising viral technique for CF patients, as they are able to integrate DNA into the host genome and persistently express the new CFTR copy. As for non-viral vector systems, nanoparticle delivery systems are emerging due to their enhanced delivery efficiency.
How does cystic fibrosis affect the body?
Cystic fibrosis (CF) is a genetic disease caused by a mutation in the transmembrane conductance regulator gene, or CFTR. 1 The CFTR gene codes for the CFTR protein, which regulates the chloride channel and helps move chloride ions to the cell surface. 2 Without the chloride ion at the surface to attract water, mucus in various organs builds up and becomes very thick and sticky. 2 In the lungs of people who have CF, bacteria can get stuck in the build-up of mucus, which can cause inflammation, infection, and respiratory failure. 2 While current treatments help ease the symptoms, there is no cure for cystic fibrosis. Advancements in treatments have allowed patients to live a longer life if treatment is distributed early and managed consistently. 2
Is lentivirus a viral vector?
Currently, lentivirus vectors are a promising viral technique for CF patients, as well as nanoparticle delivery systems due to their enhanced gene expression and delivery efficiency. While the implementation of a cystic fibrosis gene therapy technique has been more challenging than previously expected, new research continues to bring ...
Is cystic fibrosis gene therapy FDA approved?
However, even after years of clinical trials, there is still no FDA approved cystic fibrosis gene therapy technique. Researchers have found difficulty finding a vector system that has maintained high levels of expression over an extended period of time. This review investigates the early and current development of vector delivery systems, ...
Is there a gene therapy for cystic fibrosis?
Since the discovery of the CFTR gene, researchers have been working to develop a gene therapy technique that helps to correct the causative gene in cystic fibrosis patients. Many vector delivery systems have been researched. However, even after years of clinical trials, there is still no FDA approved cystic fibrosis gene therapy technique.
Is cystic fibrosis an incurable disease?
While cystic fibrosis is an incurable inherited disease, researchers have come a long way to developing effective treatments that have increased the quality and lifetime of diagnosed individuals. The field of genetics is progressively learning from the extended research done on gene therapy including viral and non-viral vectors and new vectors that can efficiently deliver and correct the CFTR channel defect. 5-6, 8, 12-14 Major vector delivery systems are outlined in Table 1. The development of a more effective DNA delivery system for genetically altering more airway cells, however, is needed if treatment based on gene therapy is to be achieved. The lentivirus vectors are a promising viral technique for CF patients, as they are able to integrate DNA into the host genome and persistently express the new CFTR copy. As for non-viral vector systems, nanoparticle delivery systems are emerging due to their enhanced delivery efficiency. Ideally, a vector should have high transduction efficiency, display a high safety profile which can be administrated without any genotoxic effects, and be relatively inexpensive. Therefore, future research should focus on improving vector designs and delivery systems, specifically the lentivirus vectors and nanoparticle systems, and the medical field will be on its way to creating new gene therapeutic techniques for patients with cystic fibrosis, as well as other diseases.
Current Treatment of Cystic Fibrosis
CF is an autosomal recessive monogenetic disease that is caused by a mutation in cystic fibrosis transmembrane conductance regulator ( CFTR ), a gene responsible for the production of sweat, digestive fluids, and mucus.
AAV Vector-Based Gene Therapy for Cystic Fibrosis
As a monogenetic disorder (loss function of CFTR protein), CF makes an ideal candidate for gene therapy. Human CFTR cDNA delivery into cells by AAV vectors to reverse the pathological phenotype caused by protein dysfunction is a preferred choice.