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Immunology of AAV-Mediated Gene Transfer in the Eye.

Willett K, Bennett J - Front Immunol (2013)

Bottom Line: Encouragingly, AAV appears safe and effective with clinical follow-up surpassing 5 years in some studies.As disease targets continue to expand for AAV in the eye, thorough and deliberate assessment of immunologic safety is critical.With careful study, the development of these technologies should concurrently inform the biology of the ocular immune response.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Scheie Eye Institute, F.M. Kirby Center for Molecular Ophthalmology, University of Pennsylvania , Philadelphia, PA , USA.

ABSTRACT
The eye has been at the forefront of translational gene therapy largely owing to suitable disease targets, anatomic accessibility, and well-studied immunologic privilege. These advantages have fostered research culminating in several clinical trials and adeno-associated virus (AAV) has emerged as the vector of choice for many ocular therapies. Pre-clinical and clinical investigations have assessed the humoral and cellular immune responses to a variety of naturally occurring and engineered AAV serotypes as well as their delivered transgenes and these data have been correlated to potential clinical sequelae. Encouragingly, AAV appears safe and effective with clinical follow-up surpassing 5 years in some studies. As disease targets continue to expand for AAV in the eye, thorough and deliberate assessment of immunologic safety is critical. With careful study, the development of these technologies should concurrently inform the biology of the ocular immune response.

No MeSH data available.


Related in: MedlinePlus

Clinical trials of ocular AAV registered on www.clinicaltrials.gov. Searched as search term = eye and interventions = adeno-associated virus OR AAV OR rAAV. Number of patients reported as actual or planned numbers for enrollment.
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Figure 2: Clinical trials of ocular AAV registered on www.clinicaltrials.gov. Searched as search term = eye and interventions = adeno-associated virus OR AAV OR rAAV. Number of patients reported as actual or planned numbers for enrollment.

Mentions: Other viruses such as lentivirus and adenovirus have been or are currently under investigation for ocular gene delivery. Compared to these viral and also non-viral modes of gene transfer, recombinant AAV continues to be a popular vector used in the eye both in basic science and translational studies (Figure 1). At present, clinical trials involving ocular administration of AAV are ongoing on four continents with an aggregate enrollment of over 200 participants (Figure 2). AAV, a helper-dependent single-stranded DNA parvovirus has never been shown to cause disease in humans or animals. It is appealing as a vector because it can stably and efficiently induce gene expression in dividing or terminally differentiated cells, has a favorable toxicity profile and benign immune response. Also, manipulation of the AAV capsid as well as promoters in the cDNA transgene effectively modulate cellular tropism which is critical to the cell-specific pathophysiology of many eye diseases (5).


Immunology of AAV-Mediated Gene Transfer in the Eye.

Willett K, Bennett J - Front Immunol (2013)

Clinical trials of ocular AAV registered on www.clinicaltrials.gov. Searched as search term = eye and interventions = adeno-associated virus OR AAV OR rAAV. Number of patients reported as actual or planned numbers for enrollment.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3757345&req=5

Figure 2: Clinical trials of ocular AAV registered on www.clinicaltrials.gov. Searched as search term = eye and interventions = adeno-associated virus OR AAV OR rAAV. Number of patients reported as actual or planned numbers for enrollment.
Mentions: Other viruses such as lentivirus and adenovirus have been or are currently under investigation for ocular gene delivery. Compared to these viral and also non-viral modes of gene transfer, recombinant AAV continues to be a popular vector used in the eye both in basic science and translational studies (Figure 1). At present, clinical trials involving ocular administration of AAV are ongoing on four continents with an aggregate enrollment of over 200 participants (Figure 2). AAV, a helper-dependent single-stranded DNA parvovirus has never been shown to cause disease in humans or animals. It is appealing as a vector because it can stably and efficiently induce gene expression in dividing or terminally differentiated cells, has a favorable toxicity profile and benign immune response. Also, manipulation of the AAV capsid as well as promoters in the cDNA transgene effectively modulate cellular tropism which is critical to the cell-specific pathophysiology of many eye diseases (5).

Bottom Line: Encouragingly, AAV appears safe and effective with clinical follow-up surpassing 5 years in some studies.As disease targets continue to expand for AAV in the eye, thorough and deliberate assessment of immunologic safety is critical.With careful study, the development of these technologies should concurrently inform the biology of the ocular immune response.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Scheie Eye Institute, F.M. Kirby Center for Molecular Ophthalmology, University of Pennsylvania , Philadelphia, PA , USA.

ABSTRACT
The eye has been at the forefront of translational gene therapy largely owing to suitable disease targets, anatomic accessibility, and well-studied immunologic privilege. These advantages have fostered research culminating in several clinical trials and adeno-associated virus (AAV) has emerged as the vector of choice for many ocular therapies. Pre-clinical and clinical investigations have assessed the humoral and cellular immune responses to a variety of naturally occurring and engineered AAV serotypes as well as their delivered transgenes and these data have been correlated to potential clinical sequelae. Encouragingly, AAV appears safe and effective with clinical follow-up surpassing 5 years in some studies. As disease targets continue to expand for AAV in the eye, thorough and deliberate assessment of immunologic safety is critical. With careful study, the development of these technologies should concurrently inform the biology of the ocular immune response.

No MeSH data available.


Related in: MedlinePlus