‘Bespoke Gene Therapy Consortium’ sets out to enable gene therapies for ultra-rare diseases

2021 ◽  
Author(s):  
Katie Kingwell
Keyword(s):  
Gene Therapy ◽  
Rare Diseases ◽  
Gene Therapies

scholarly journals The Ocular Gene Delivery Landscape

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1135
Author(s):  
Bhubanananda Sahu ◽  
Isha Chug ◽  
Hemant Khanna
Keyword(s):  
Gene Therapy ◽  
Genetic Diseases ◽  
Gene Therapies ◽  
Advantages And Disadvantages ◽  
Fda Approval ◽  
New Information ◽  
Efficient Delivery ◽  
Delivery Routes ◽  
History Of ◽  
Different Parts

The eye is at the forefront of developing therapies for genetic diseases. With the FDA approval of the first gene-therapy drug for a form of congenital blindness, numerous studies have been initiated to develop gene therapies for other forms of eye diseases. These examinations have revealed new information about the benefits as well as restrictions to using drug-delivery routes to the different parts of the eye. In this article, we will discuss a brief history of gene therapy and its importance to the eye and ocular delivery landscape that is currently being investigated, and provide insights into their advantages and disadvantages. Efficient delivery routes and vehicle are crucial for an effective, safe, and longer-lasting therapy.

scholarly journals Characterization of Recombinant Adeno-Associated Viruses (rAAVs) for Gene Therapy Using Orthogonal Techniques

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 586
Author(s):  
Liam Cole ◽  
Diogo Fernandes ◽  
Maryam T. Hussain ◽  
Michael Kaszuba ◽  
John Stenson ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Light Scattering ◽  
Dynamic Light Scattering ◽  
Viral Vector ◽  
Structural Characteristics ◽  
Genetic Material ◽  
Label Free ◽  
Gene Therapies ◽  
Multiple Challenges

Viruses are increasingly used as vectors for delivery of genetic material for gene therapy and vaccine applications. Recombinant adeno-associated viruses (rAAVs) are a class of viral vector that is being investigated intensively in the development of gene therapies. To develop efficient rAAV therapies produced through controlled and economical manufacturing processes, multiple challenges need to be addressed starting from viral capsid design through identification of optimal process and formulation conditions to comprehensive quality control. Addressing these challenges requires fit-for-purpose analytics for extensive characterization of rAAV samples including measurements of capsid or particle titer, percentage of full rAAV particles, particle size, aggregate formation, thermal stability, genome release, and capsid charge, all of which may impact critical quality attributes of the final product. Importantly, there is a need for rapid analytical solutions not relying on the use of dedicated reagents and costly reference standards. In this study, we evaluate the capabilities of dynamic light scattering, multiangle dynamic light scattering, and SEC–MALS for analyses of rAAV5 samples in a broad range of viral concentrations (titers) at different levels of genome loading, sample heterogeneity, and sample conditions. The study shows that DLS and MADLS® can be used to determine the size of full and empty rAAV5 (27 ± 0.3 and 33 ± 0.4 nm, respectively). A linear range for rAAV5 size and titer determination with MADLS was established to be 4.4 × 1011–8.7 × 1013 cp/mL for the nominally full rAAV5 samples and 3.4 × 1011–7 × 1013 cp/mL for the nominally empty rAAV5 samples with 3–8% and 10–37% CV for the full and empty rAAV5 samples, respectively. The structural stability and viral load release were also inferred from a combination of DLS, SEC–MALS, and DSC. The structural characteristics of the rAAV5 start to change from 40 °C onward, with increasing aggregation observed. With this study, we explored and demonstrated the applicability and value of orthogonal and complementary label-free technologies for enhanced serotype-independent characterization of key properties and stability profiles of rAAV5 samples.

scholarly journals Estimating the Financial Impact of Gene Therapy*

2020 ◽  
Author(s):  
Chi Heem Wong ◽  
Dexin Li ◽  
Nina Wang ◽  
Jonathan Gruber ◽  
Rena Conti ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Time Horizon ◽  
Financial Impact ◽  
Age Group ◽  
Patient Access ◽  
Quality Adjusted Life Years ◽  
Gene Therapies ◽  
Life Years ◽  
Expected Benefits ◽  
Quality Adjusted Life

AbstractWe assess the potential financial impact of future gene therapies by identifying the 109 late-stage gene therapy clinical trials currently underway, estimating the prevalence and incidence of their corresponding diseases, developing novel mathematical models of the increase in quality-adjusted life years for each approved gene therapy, and simulating the launch prices and the expected spending of these therapies over a 15-year time horizon. The results of our simulation suggest that an expected total of 1.09 million patients will be treated by gene therapy from January 2020 to December 2034. The expected peak annual spending on these therapies is $25.3 billion, and the total spending from January 2020 to December 2034 is $306 billion. We decompose their annual estimated spending by treated age group as a proxy for U.S. insurance type, and consider the tradeoffs of various methods of payment for these therapies to ensure patient access to their expected benefits.

scholarly journals The Promise and the Hope of Gene Therapy

2021 ◽  
Vol 3 ◽  
Author(s):  
Eleni Papanikolaou ◽  
Andreas Bosio
Keyword(s):  
Gene Therapy ◽  
Hemopoietic Stem Cell ◽  
Cell Therapies ◽  
Gene Therapies ◽  
Monogenic Diseases ◽  
Car T ◽  
The Everyday ◽  
Cell Gene ◽  
Stem Cell Gene Therapy

It has been over 30 years since visionary scientists came up with the term “Gene Therapy,” suggesting that for certain indications, mostly monogenic diseases, substitution of the missing or mutated gene with the normal allele via gene addition could provide long-lasting therapeutic effect to the affected patients and consequently improve their quality of life. This notion has recently become a reality for certain diseases such as hemoglobinopathies and immunodeficiencies and other monogenic diseases. However, the therapeutic wave of gene therapies was not only applied in this context but was more broadly employed to treat cancer with the advent of CAR-T cell therapies. This review will summarize the gradual advent of gene therapies from bench to bedside with a main focus on hemopoietic stem cell gene therapy and genome editing and will provide some useful insights into the future of genetic therapies and their gradual integration in the everyday clinical practice.

scholarly journals Evading the AAV Immune Response in Mucopolysaccharidoses

2020 ◽  
Vol 21 (10) ◽  
pp. 3433
Author(s):  
Matthew Piechnik ◽  
Kazuki Sawamoto ◽  
Hidenori Ohnishi ◽  
Norio Kawamoto ◽  
Yasuhiko Ago ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Immune Response ◽  
Humoral Immune Response ◽  
Transgene Expression ◽  
Evidence Based ◽  
Adeno Associated Virus ◽  
Gene Therapies ◽  
Humoral Immune ◽  
Significant Challenge ◽  
Racial Background

The humoral immune response elicited by adeno-associated virus (AAV)-mediated gene therapy for the treatment of mucopolysaccharidoses (MPS) poses a significant challenge to achieving therapeutic levels of transgene expression. Antibodies targeting the AAV capsid as well as the transgene product diminish the production of glycosaminoglycan (GAG)-degrading enzymes essential for the treatment of MPS. Patients who have antibodies against AAV capsid increase in number with age, serotype, and racial background and are excluded from the clinical trials at present. In addition, patients who have undergone AAV gene therapy are often excluded from the additional AAV gene therapy with the same serotype, since their acquired immune response (antibody) against AAV will limit further efficacy of treatment. Several methods are being developed to overcome this immune response, such as novel serotype design, antibody reduction by plasmapheresis and immunosuppression, and antibody evasion using empty capsids and enveloped AAV vectors. In this review, we examine the mechanisms of the anti-AAV humoral immune response and evaluate the strengths and weaknesses of current evasion strategies in order to provide an evidence-based recommendation on evading the immune response for future AAV-mediated gene therapies for MPS.

scholarly journals The role of hypoxia-inducible factors in neovascular age-related macular degeneration: a gene therapy perspective

2019 ◽  
Vol 77 (5) ◽  
pp. 819-833 ◽  
Author(s):  
Parviz Mammadzada ◽  
Pablo M. Corredoira ◽  
Helder André
Keyword(s):  
Gene Therapy ◽  
Macular Degeneration ◽  
Clinical Phenotype ◽  
Therapeutic Strategies ◽  
Age Related Macular Degeneration ◽  
Hypoxia Inducible Factors ◽  
Ocular Angiogenesis ◽  
Gene Therapies ◽  
Age Related

AbstractUnderstanding the mechanisms that underlie age-related macular degeneration (AMD) has led to the identification of key molecules. Hypoxia-inducible transcription factors (HIFs) have been associated with choroidal neovascularization and the progression of AMD into the neovascular clinical phenotype (nAMD). HIFs regulate the expression of multiple growth factors and cytokines involved in angiogenesis and inflammation, hallmarks of nAMD. This knowledge has propelled the development of a new group of therapeutic strategies focused on gene therapy. The present review provides an update on current gene therapies in ocular angiogenesis, particularly nAMD, from both basic and clinical perspectives.

scholarly journals Gene Therapy for Liver Cancers: Current Status from Basic to Clinics

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1865 ◽  
Author(s):  
Kenya Kamimura ◽  
Takeshi Yokoo ◽  
Hiroyuki Abe ◽  
Shuji Terai
Keyword(s):  
Gene Therapy ◽  
Liver Cancer ◽  
Liver Diseases ◽  
Malignant Tumors ◽  
Therapeutic Options ◽  
Endocrine Function ◽  
Current Status ◽  
Congenital Disease ◽  
Gene Therapies ◽  
Liver Cancers

The liver is a key organ for metabolism, protein synthesis, detoxification, and endocrine function, and among liver diseases, including hepatitis, cirrhosis, malignant tumors, and congenital disease, liver cancer is one of the leading causes of cancer-related deaths worldwide. Conventional therapeutic options such as embolization and chemotherapy are not effective against advanced-stage liver cancer; therefore, continuous efforts focus on the development of novel therapeutic options, including molecular targeted agents and gene therapy. In this review, we will summarize the progress toward the development of gene therapies for liver cancer, with an emphasis on recent clinical trials and preclinical studies.

scholarly journals Critical Aspects of Clinical Trial Design for Novel Cell and Gene Therapies

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Zinovia Kefalopoulou ◽  
Iciar Aviles-Olmos ◽  
Thomas Foltynie
Keyword(s):  
Gene Therapy ◽  
Viral Vector ◽  
Safety Data ◽  
Clinical Trial Design ◽  
Open Label ◽  
Double Blind ◽  
Gene Therapies ◽  
Technological Advances ◽  
Vector Gene Transfer ◽  
Cell And Gene Therapy

Neural cell transplantation and gene therapy have attracted considerable interest as promising therapeutic alternatives for patients with Parkinson's disease (PD). Preclinical and open-label studies have suggested that grafted fetal neural tissue or viral vector gene transfer can achieve considerable biochemical and clinical improvements, whereas subsequent double-blind, placebo-controlled protocols have produced rather more modest and variable results. Detailed evaluation of these discordant findings has highlighted several crucial issues such as patient selection criteria, details surrounding transplantation or gene therapy methodologies, as well as the study designs themselves that ought to be carefully considered in the planning phases of future clinical trials. Beyond the provision of symptomatic efficacy and safety data, it also remains to be identified whether the possibilities offered by stem cell and gene therapy technological advances might translate to meaningful neuroprotection and/or disease-modifying effects or alleviate the nonmotor aspects of PD and thus offer additional benefits beyond those achieved through conventional pharmacotherapy or deep brain stimulation (DBS).

scholarly journals Gene Therapy for Rare Diseases: Summary of a National Institutes of Health Workshop, September 13, 2012

2013 ◽  
Vol 24 (4) ◽  
pp. 355-362 ◽  
Author(s):  
Marina O'Reilly ◽  
Donald B. Kohn ◽  
Jeffrey Bartlett ◽  
Janet Benson ◽  
Philip J. Brooks ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Rare Diseases ◽  
National Institutes Of Health

scholarly journals Nonclinical Studies that Support Viral Vector-Delivered Gene Therapies: An EFPIA Gene Therapy Working Group Perspective

2020 ◽  
Vol 19 ◽  
pp. 89-98
Author(s):  
Michael W. Bolt ◽  
Laurence O. Whiteley ◽  
Jessica L. Lynch ◽  
Brian Lauritzen ◽  
Antonio R. Fernández de Henestrosa ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Working Group ◽  
Viral Vector ◽  
Gene Therapies
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