scholarly journals U.S-Based Community Oncologists/Hematologists' Perceptions Regarding Future Use of Gene Therapies for Patients with Hematological Disorders

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2986-2986
Author(s):  
Ajeet Gajra ◽  
Stephanie Fortier ◽  
Yolaine Jeune-Smith ◽  
Bruce A. Feinberg
Keyword(s):  
Gene Therapy ◽  
Clinical Practice ◽  
Genetic Material ◽  
Comfort Level ◽  
Significant Advance ◽  
Barriers To Adoption ◽  
Gene Therapies ◽  
Car T ◽  
Prohibitive Cost ◽  
The U.S

Abstract Introduction Gene therapies, defined as the introduction, removal, or change in genetic material into a patient's cells to treat a specific disease, represent a significant advance in medicine, with the potential to cure or significantly improve outcomes of various benign and malignant hematologic disorders (American Society of Gene Therapy). Gene therapies have received approvals for subsets of patients with spinal muscular atrophy or retinal dystrophy, and almost a thousand studies are actively recruiting patients for various gene therapy trials. Aside from CAR-T therapies, several gene therapies are in advanced clinical development in the U.S. for disorders such as hemophilia, hemoglobinopathies, and congenital immunodeficiency syndromes. Results of many such trials were presented at the 2020 ASH annual meeting. While approvals for some gene therapy products are expected in the near future, the complexity of treatment, knowledge gaps among providers, or barriers with accessibility or cost may limit the integration of these treatments into routine clinical practice. Therefore, the present study surveyed U.S.-based community oncologists/hematologists (cO/H) to evaluate their perceptions of the utility of gene therapies and barriers to adoption or integration into clinical practice. Methods Between February and April 2021, cO/H from across the U.S. were invited to complete a web-based survey about gene therapies. Physician demographics and practice characteristics were also captured in the survey. Responses were aggregated and analyzed using descriptive statistics. Results A total of 369 cO/H completed the survey; 36% identified as a medical oncologist and 63% as a hematologist/oncologist. cO/H had an average of 19 years of clinical experience and spent an average of 86% of their working time in direct patient care and saw an average of 17 patients per day on clinic days. Half of cO/H stated that they were not aware of recent data of gene therapies for adult hematology/oncology indications (35% "not very aware"; 15% "not at all aware"). When asked to report the number of approved gene therapy products (excluding CAR-T products) in the U.S. in early 2021, 27% of participants reported 0, 24% reported 1, and 20% reported 2 products were currently available. Regarding gene therapy use for adult hematologic/oncologic indications in the next 2 years, 53% of cO/H reported that they expect gene therapies to mostly be administered and managed by academic centers to which they will refer their patients; 27% reported that indications will be limited and unlikely to affect their practice (Table 1). cO/H perceived cost as the greatest barrier to adopting gene therapies into their clinical practice; specifically, cO/H cited cost limitations by payers (49%), the prohibitive cost to patients (46%), and the prohibitive cost to practices/hospitals (37%). Other barriers to adoption were limited real-world efficacy data (18%) and long-term complications (13%). Most cO/H reported a moderate (39%) or high (43%) comfort level with prescribing a gene therapy for adult hematology/oncology indications if it were reimbursed. Conclusions Many cO/H were not aware of recent data of gene therapy products, with over half expecting to refer their patients to large academic centers for gene therapies. While most cO/H would be comfortable prescribing gene therapies for their patients, cost was perceived as prohibitive. This information can inform various stakeholders, including patients, advocacy groups, pharmaceutical manufacturers, payers, and professional societies, in laying the foundations for gene therapy products in hematology. Future work should focus on enhancing education of gene therapy products to community providers as well as identifying support programs that lessen the burden of cost. Figure 1 Figure 1. Disclosures Gajra: Cardinal Health: Current Employment, Current equity holder in publicly-traded company. Fortier: Cardinal Health: Current Employment. Jeune-Smith: Cardinal Health: Current Employment. Feinberg: Cardinal Health: Current Employment.

scholarly journals How Far Are Non-Viral Vectors to Come of Age and Reach Clinical Translation in Gene Therapy?

2021 ◽  
Vol 22 (14) ◽  
pp. 7545
Author(s):  
Myriam Sainz-Ramos ◽  
Idoia Gallego ◽  
Ilia Villate-Beitia ◽  
Jon Zarate ◽  
Iván Maldonado ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Clinical Practice ◽  
Gene Delivery ◽  
Viral Vectors ◽  
Viral Vector ◽  
Clinical Success ◽  
Genetic Material ◽  
Viral Gene ◽  
Promising Alternative ◽  
Vector Systems

Efficient delivery of genetic material into cells is a critical process to translate gene therapy into clinical practice. In this sense, the increased knowledge acquired during past years in the molecular biology and nanotechnology fields has contributed to the development of different kinds of non-viral vector systems as a promising alternative to virus-based gene delivery counterparts. Consequently, the development of non-viral vectors has gained attention, and nowadays, gene delivery mediated by these systems is considered as the cornerstone of modern gene therapy due to relevant advantages such as low toxicity, poor immunogenicity and high packing capacity. However, despite these relevant advantages, non-viral vectors have been poorly translated into clinical success. This review addresses some critical issues that need to be considered for clinical practice application of non-viral vectors in mainstream medicine, such as efficiency, biocompatibility, long-lasting effect, route of administration, design of experimental condition or commercialization process. In addition, potential strategies for overcoming main hurdles are also addressed. Overall, this review aims to raise awareness among the scientific community and help researchers gain knowledge in the design of safe and efficient non-viral gene delivery systems for clinical applications to progress in the gene therapy field.

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 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 Delivering cellular and gene therapies to patients: solutions for realizing the potential of the next generation of medicine

Gene Therapy ◽  
2019 ◽  
Vol 27 (12) ◽  
pp. 537-544 ◽  
Author(s):  
Kris Elverum ◽  
Maria Whitman
Keyword(s):  
Gene Therapy ◽  
Small Molecules ◽  
Drug Administration ◽  
Business Models ◽  
Next Generation ◽  
Call To Action ◽  
Gene Therapies ◽  
Therapeutic Benefits ◽  
Successful Business ◽  
The U.S

AbstractThe evolution of medicines from small molecules to proteins drove increased therapeutic benefits, and the next generation of cell and gene therapies holds tremendous promise for patients. The Food and Drug Administration approved the U.S.’s first gene therapy, Novartis’ tisagenlecleucel, and technologies like CRISPR-Cas9 are poised to create a wave of new medicines. Unfortunately, the vast majority of patients may not benefit from cell and gene therapies. At least 95% of people receive medicines only through commercial delivery, but stakeholders have struggled to develop and sustain successful business models for cell and gene therapies. This paper reviews the existing system to deliver cell and gene therapies and outlines the requirements to make them accessible to patients. Informed by interviews with experts, opportunities for improvement are identified along the patient and cell journeys, and a call to action is made for stakeholders to detail and implement change.

scholarly journals Recent Advances in Preclinical Research Using PAMAM Dendrimers for Cancer Gene Therapy

2021 ◽  
Vol 22 (6) ◽  
pp. 2912
Author(s):  
Piotr Tarach ◽  
Anna Janaszewska
Keyword(s):  
Gene Therapy ◽  
Clinical Setting ◽  
Transfection Efficiency ◽  
Genetic Material ◽  
Three Dimensional ◽  
Pamam Dendrimers ◽  
Preclinical Research ◽  
Viral Origin ◽  
Gene Therapies ◽  
Advantages And Disadvantages

Carriers of genetic material are divided into vectors of viral and non-viral origin. Viral carriers are already successfully used in experimental gene therapies, but despite advantages such as their high transfection efficiency and the wide knowledge of their practical potential, the remaining disadvantages, namely, their low capacity and complex manufacturing process, based on biological systems, are major limitations prior to their broad implementation in the clinical setting. The application of non-viral carriers in gene therapy is one of the available approaches. Poly(amidoamine) (PAMAM) dendrimers are repetitively branched, three-dimensional molecules, made of amide and amine subunits, possessing unique physiochemical properties. Surface and internal modifications improve their physicochemical properties, enabling the increase in cellular specificity and transfection efficiency and a reduction in cytotoxicity toward healthy cells. During the last 10 years of research on PAMAM dendrimers, three modification strategies have commonly been used: (1) surface modification with functional groups; (2) hybrid vector formation; (3) creation of supramolecular self-assemblies. This review describes and summarizes recent studies exploring the development of PAMAM dendrimers in anticancer gene therapies, evaluating the advantages and disadvantages of the modification approaches and the nanomedicine regulatory issues preventing their translation into the clinical setting, and highlighting important areas for further development and possible steps that seem promising in terms of development of PAMAM as a carrier of genetic material.

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 Liquid Biopsy in Pancreatic Cancer: Are We Ready to Apply It in the Clinical Practice?

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1986
Author(s):  
Victoria Heredia-Soto ◽  
Nuria Rodríguez-Salas ◽  
Jaime Feliu
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Practice ◽  
Early Diagnosis ◽  
Minimally Invasive ◽  
Liquid Biopsy ◽  
Genetic Material ◽  
Current Status ◽  
Ductal Adenocarcinoma ◽  
Disease Monitoring ◽  
Global Status

Pancreatic ductal adenocarcinoma (PDAC) exhibits the poorest prognosis of all solid tumors, with a 5-year survival of less than 10%. To improve the prognosis, it is necessary to advance in the development of tools that help us in the early diagnosis, treatment selection, disease monitoring, evaluation of the response and prognosis. Liquid biopsy (LB), in its different modalities, represents a particularly interesting tool for these purposes, since it is a minimally invasive and risk-free procedure that can detect both the presence of genetic material from the tumor and circulating tumor cells (CTCs) in the blood and therefore distantly reflect the global status of the disease. In this work we review the current status of the main LB modalities (ctDNA, exosomes, CTCs and cfRNAs) for detecting and monitoring PDAC.

The Promise and Challenges of CAR-T Gene Therapy

JAMA ◽  
2017 ◽  
Vol 318 (22) ◽  
pp. 2167 ◽  
Author(s):  
Bridget M. Kuehn
Keyword(s):  
Gene Therapy ◽  
Car T

Growth factor gene therapy for Alzheimer disease

2002 ◽  
Vol 13 (5) ◽  
pp. 1-5 ◽  
Author(s):  
Mark H. Tuszynski ◽  
Hoi Sang U ◽  
John Alksne ◽  
Roy A. Bakay ◽  
Mary Margaret Pay ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Nervous System ◽  
Growth Factors ◽  
Growth Factor ◽  
Alzheimer Disease ◽  
Neuronal Degeneration ◽  
Significant Advance ◽  
Factor Gene ◽  
Growth Factor Gene ◽  
Effective Manner

The capacity to prevent neuronal degeneration and death during the course of progressive neurological disorders such as Alzheimer disease (AD) would represent a significant advance in therapy. Nervous system growth factors are families of naturally produced proteins that, in animal models, exhibit extensive potency in preventing neuronal death due to a variety of causes, reversing age-related atrophy of neurons, and ameliorating functional deficits. The main challenge in translating growth factor therapy to the clinic has been delivery of growth factors to the brain in sufficient concentrations to influence neuronal function. One means of achieving growth factor delivery to the central nervous system in a highly targeted, effective manner may be gene therapy. In this article the authors summarize the development and implementation of nerve growth factor gene delivery as a potential means of reducing cell loss in AD.

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