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How Gene Therapy Works

Gene therapy involves modifying a patient’s own cells to treat or cure a disease. This is done by introducing a new or modified gene into the patient’s cells, which can correct a genetic defect or produce a therapeutic protein. There are two main types of gene therapy: somatic gene therapy and germline gene therapy.

Somatic gene therapy involves modifying cells that are not involved in reproduction, such as skin cells or blood cells. This type of gene therapy is the most common and has been used to treat a variety of diseases, including genetic disorders, certain types of cancer, and autoimmune diseases. Germline gene therapy, on the other hand, involves modifying the genes in reproductive cells, such as sperm or egg cells. This type of gene therapy is still in the experimental stage and is not yet approved for use in humans.

The most common method of gene therapy is to use a virus to deliver the new or modified gene into the patient’s cells. Viruses are ideal for this purpose because they naturally enter cells and can be modified to carry the desired gene. Once the virus enters the patient’s cells, it delivers the new or modified gene, which then produces the therapeutic protein or corrects the genetic defect.

Benefits of Gene Therapy

Gene therapies have the potential to treat and cure a wide range of diseases, including genetic disorders, cancer, and autoimmune diseases. One of the biggest advantages of gene therapy is that it targets the underlying cause of the disease, rather than just treating the symptoms. This means that gene therapy has the potential to provide long-term or even permanent relief from a disease.

Gene therapy also has the advantage of being highly targeted. Because the therapy is delivered directly to the patient’s cells, it can be designed to target only the cells that are affected by the disease. This can minimize side effects and improve the effectiveness of the treatment.

Another advantage of gene therapy is that it can be used in combination with other treatments. For example, gene therapy can be used to sensitize cancer cells to chemotherapy or radiation therapy, making these treatments more effective.

Challenges in Gene Therapy Development

Despite the potential benefits of gene therapy, there are many challenges to overcome in its development. One of the biggest challenges is ensuring the safety and efficacy of the therapy. Because gene therapy involves modifying a patient’s own cells, there is a risk of unintended consequences, such as the development of cancer or an immune response to the therapy.

Another challenge is the cost of gene therapy. Because the therapy is highly targeted and personalized, it can be expensive to produce and administer. This can make it difficult to make the therapy available to everyone who could benefit from it.

Finally, there is still much to learn about the long-term effects of gene therapy. Because the therapy is still a relatively new field, there is limited data on the long-term effects of the therapy. This makes it difficult to assess the risks and benefits of the therapy over the long term.

Regulatory Landscape in India for Gene Therapies

In India, the use of gene therapy is allowed, but it requires approval from the Central Drugs Standard Control Organisation (CDSCO), which is responsible for regulating drugs and medical devices.

To promote the development of safe and effective gene therapy products, the CDSCO issued guidelines in 2019 to establish a regulatory framework for gene therapy. These guidelines aim to standardize gene therapy product development and clinical trials and require long-term follow-up of at least five years for all clinical trials. Additionally, up to 10 years of follow-up is recommended after commercialization to ensure continued safety and efficacy.

To provide expert oversight, the government proposed the creation of an independent body of biomedical and gene therapy experts, called The Gene Therapy and Advisory and Evaluation Committee (GTEAC), in 2019. This committee supervises proposed therapies and provide guidance to ensure they meet safety and ethical standards.

Approval process: Gene and cell therapy products need to obtain regulatory approval from the CDSCO before they can be marketed or used in clinical trials. The approval process involves submission of a detailed application, including preclinical and clinical data, manufacturing and quality control information, and ethical considerations.

The National Ethical Guidelines for Biomedical and Health Research Involving Human Participants applies to all clinical trials involving human participants, including gene therapy trials. These guidelines These guidelines cover aspects such as trial design, patient selection, informed consent, safety monitoring, and reporting of adverse events. These are based on principles to ensure the safety and dignity of human participants, such as the right to privacy and the principle of voluntariness.

Manufacturing and quality control: Gene and cell therapy products need to be manufactured and tested according to the Good Manufacturing Practices (GMP) guidelines issued by the CDSCO. These guidelines cover aspects such as facility design, personnel, equipment, and quality control procedures.

Post-marketing surveillance: Gene and cell therapy products need to be monitored for safety and efficacy after they are approved for marketing. The CDSCO has set up a Pharmacovigilance Program to monitor the safety of drugs and biological products, including gene and cell therapy products.  

It is essential that researchers and developers follow these guidelines to ensure that gene therapy trials are conducted ethically and safely.

Ethical Considerations in Gene Therapy

Gene therapy raises a number of ethical considerations, particularly with regard to germline gene therapy. One of the main concerns is the potential for unintended consequences, such as the development of cancer or an immune response to the therapy. Another concern is the potential for the therapy to be used for non-therapeutic purposes, such as enhancing physical or cognitive abilities.

To address these concerns, many countries, including India, have established guidelines and regulations for the use of gene therapy in humans. These guidelines are designed to ensure that gene therapy is used only for therapeutic purposes and that the risks and benefits of the therapy are carefully evaluated.

Future Prospects for Gene Therapies in India

The future of gene therapies in India is bright. India has a large and growing biotechnology industry, with many companies and research institutions dedicated to the development of gene therapy. In addition, the Indian government has been supportive of the biotechnology industry, providing funding and incentives for research and development.

One area of particular interest is the development of gene therapy for rare diseases. Because these diseases affect a relatively small number of people, they have historically been overlooked by the pharmaceutical industry. However, gene therapy has the potential to provide a targeted and effective treatment for these diseases.

Conclusion and Key Takeaways

Gene-modified cell therapies have the potential to revolutionize the treatment of a wide range of diseases. However, there are many challenges to overcome in the development and regulation of these therapies. In India, the regulatory landscape for gene-modified cell therapies is governed by the DBT and the ICMR, and researchers must comply with their guidelines and obtain approval from the DCGI and the IEC to conduct clinical trials.

Despite the challenges, the future of gene-modified cell therapies in India is bright. The growing biotechnology industry and government support for research and development provide a strong foundation for the continued development of these therapies. In the coming years, we can expect to see significant advances in the development and use of gene therapy in India.

FDA approved Gene therapies till date 2022

If you are interested in learning more about how we can assist you in leading the way in biotech, pharma, or healthcare research and development, please do not hesitate to contact us at info@gvrp.in.

Written by: Dr. Nidhi Khurana
Dr. Nidhi Khurana holds a Ph.D. in Biotechnology and leverages her knowledge of science and marketing to build thoughtful partnerships with industry leaders. Currently, Dr. Khurana serves as the Head of Marketing at GV Research Platform, where she is responsible for driving growth and building the company’s brand. Alongside, she is passionate about writing and uses it as a medium to educate the community on the latest trends and technologies in the drug discovery and development space.

The National Medical Devices Policy, 2023 has been approved by the Union Cabinet, chaired by PM Modi, to tap the potential of the sector and facilitate an orderly growth of the medical device sector to meet the public health objectives of access, affordability, quality, and innovation.

Are you aware of the current scenario of the medical device sector in India? The medical devices sector is currently valued at $11 billion and is expected to grow to $50 billion by 2030. The National Medical Devices Policy, 2023 is expected to contribute towards achieving this goal.

The policy framework focuses on building an enabling ecosystem for manufacturing along with a focus on innovation, creating a robust and streamlined regulatory framework, providing support in training and capacity building programs, and promoting higher education to foster talent and skilled resources in line with the industry requirements. Encouraging domestic investments and production of medical devices complements the Government’s ‘Atmanirbhar Bharat’ and ‘Make in India’ programs.

The policy is expected to provide the necessary direction and support to strengthen the medical devices industry in India. It is designed to make the industry self-reliant, resilient, and competitive while meeting the evolving healthcare needs of patients. The policy covers six broad areas of policy interventions, including regulatory streamlining, enabling infrastructure, facilitating R&D and innovation, attracting investments in the sector, human resources development, and brand positioning and awareness creation.

Take a look at the six strategies that have been planned to tap the potential of the medical device sector:

Firstly, let’s talk about regulatory streamlining. In order to enhance ease of doing research and business, measures such as creating a Single Window Clearance System’ for Licensing of Medical Devices, enhancing the Role of Indian Standards like BIS, and designing a coherent pricing regulation will be followed. This will help balance patient safety with product innovation.

The next strategy is to enable infrastructure to support the growth this policy will bring in. The establishment and strengthening of large medical device parks and clusters equipped with world-class common infrastructure facilities will be pursued. These will be in proximity to economic zones with requisite logistics connectivity. This will help with better convergence and backward integration with the medical device industry. The Indian government has given its approval to set up 157 nursing colleges alongside medical colleges established in the country since 2014, at a total cost of Rs 1,570 crore.

Facilitating R&D and innovation is the third area where the policy aims to promote research and development in India by establishing centers of excellence in academic and research institutions, innovation hubs, ‘plug and play’ infrastructures and support to start-ups.

Attracting investments in the sector is another focus area of this policy. Along with recent schemes and interventions like Make in India, Ayushman Bharat program, Heal-in-India, Start-up mission, the policy encourages private investments, series of funding from Venture Capitalists, and also Public-Private Partnership(PPP).

Then comes human resources development. The policy anticipates a steady supply of skilled work force across the value chain. To achieve this, the policy will support skilling, reskilling, and upskilling of professionals in the medical device sector. It will also promote dedicated multidisciplinary courses for medical devices in existing institutions to ensure the availability of skilled manpower for futuristic medical technologies, high-end manufacturing, and research.

Lastly, brand positioning and awareness creation are critical for promoting the medical device sector. The policy foresees the creation of a dedicated Export Promotion Council for the sector under the Department, which will be an enabler to deal with various market access issues. The policy will also promote more forums to bring together various stakeholders for sharing knowledge and building strong networks across the sector.

The National Medical Devices Policy, 2023 has been welcomed by industry leaders. These strategies will provide a holistic approach to promote the medical device sector in India. The policy interventions will enhance ease of doing research and business, facilitate R&D and innovation, attract investments, and develop skilled manpower. All these measures will create a favorable ecosystem for the growth of the medical device industry in India.

Source: Express Healthcare

GVRP offers Medical Devices Testing Services.

Connect with us at info@gvrp.in to learn more about our testing services portfolio.

Written by: Dr. Nidhi Khurana
Dr. Nidhi Khurana holds a Ph.D. in Biotechnology and leverages her knowledge of science and marketing to build thoughtful partnerships with industry leaders. Currently, Dr. Khurana serves as the Head of Marketing at GV Research Platform, where she is responsible for driving growth and building the company’s brand. Alongside, she is passionate about writing and uses it as a medium to educate the community on the latest trends and technologies in the drug discovery and development space.

The search for effective cancer treatments is a never-ending battle that demands the most innovative and efficient solutions. Immunotherapy has emerged as a promising approach to combat cancer, but its complex nature and unpredictable outcomes have made it a difficult field to navigate. Unfortunately, most immunotherapy agents are not effective for 60 to 70% of cancer patients and targeting their complex immune system using in vitro screens is a daunting task.

This highlights the need for a comprehensive in vivo preclinical investigation of each new drug’s mechanism of action and efficacy for clinical applications. This is where MuScreen™ comes in, CrownBioscience’s innovative in vivo screening platform that promises to transform the way we develop immunotherapeutic drugs.

MuScreen™ offers a comprehensive suite of tools that enable scientists to test different immunotherapy medicines on mice with cancer to find the best one quickly and easily. The platform has two parts: one part tests how well the drug works on the cancer, and the other part looks at how the drug affects the mouse’s immune system. By doing so, MuScreen™ helps researchers gain a thorough understanding of a new drug’s mechanism of action and efficacy for clinical applications.

One of the key advantages of MuScreen™ is its large-scale, validated panels of homografts derived from mouse cell lines of the same inbred strain (syngeneic models) and homografts of spontaneous/ carcinogen induced GEMM (genetically engineered murine models) tumors in immunocompetent syngeneic hosts (tumor homograft models, MuPrime™). These panels can be tailored to meet specific research needs and cover a wide range of cancer types and immune profiles, making MuScreen™ a versatile and powerful tool in the fight against cancer.

In addition to its diverse range of models, MuScreen™ offers a wealth of historic data for some widely used syngeneic models, aiding support for the capabilities of the platform. The syngeneic and tumor homograft models in MuScreen™ are also comprehensively characterized, with available data including immune checkpoint inhibitor benchmarking, baseline tumor immune profile, and tumor RNAseq. Furthermore, Crown Bioscience covers the cost of the vehicle group for all models and offers a discount on shared control groups, making MuScreen™ a cost-effective solution for cancer drug development.

Maximizing the value from MuScreen™ is also possible through the FACS or Mouse I/O RNA-Seq Panel to gather further insights on immunotherapy screening. These tools enable scientists to study the pharmacodynamic effects of their immune-oncology agents, uncover predictive biomarkers, and identify patient populations that are responsive to treatment.

MuScreen™ is the most experienced, well-characterized in vivo screening platform that efficiently advances immunotherapy development. Its high-throughput and cost-effective screening across a diverse collection of immune profiles, tumor types, and mutations make MuScreen™ a distinct screening service. GVRP is the authorized distributor of Crown Bioscience services in India, and they can help you get started with MuScreen™ for your projects. With MuScreen™, the fight against cancer has never been more within reach.

Written by: Supriya Avatapalli
Sai Supriya has a 2 year experience in academic research and fair exposure to transition into industry. She enjoys delving deep into the new developments in the biotech, pharma industry and collaborating with people. She is zealous and keen to direct her best strengths to the role by being receptive to new ideas and challenges.

Edited by: Dr Nidhi Khurana

OmniScreen™ is a high throughput screening service for multiple oncology drug compounds in a single-go (lead compounds) across a diverse set of cancer cell-lines. It is your best shot to assess the early efficacy and potency of your oncology drug candidates by running initial screens with large-scale cancer cell line panels saving you cost and time.

This technology groups cell lines together based on specific characteristics suitable to the study. It offers diverse quality-controlled screening panels for you to screen your drug compounds in targeted manner. These panels include-

OmniPanel™ – It is a growing collection of >520 cancer cell lines for drug response screening providing complete analysis of the drug compound in vitro.

XenoSelect™ – This panel consists of >210 cancer cell lines and respective xenograft models to rapidly proceed to in vivo pharmacology studies.

RNAseq Panel which includes >240 cancer cell-lines with in-house genomic data such as mutation status, copy number variation and expression levels because of drug response.

PrimePanel™ – It comprises a growing collection of >30 unique primary cancer cell lines derived from PDX (patient-derived tumour tissues for in vitro screening). The ease to link this in vitro data to in vivo and further to clinical efficacy is a speciality of this subpanel enabling discovery of some predictive biomarkers.

XenoBase® is a database with curation of >1000 cancer-lines, can be used to build a custom panel and enhance your usability.

You can take control of your experiment with OmniScreen™ and get unrivaled flexibility to design the screening panels you need. The study can further be customised with flexible template designs by adjusting or extending incubation times and obtaining multiple sets of data from the test samples.

Crown Bioscience, the company behind this technology, ensures that screening results between cancer cell types are consistent by keeping a strict check on:

• Cell line quality – Annotated, well-characterized, SNP/STR verified, mycoplasma tested

• Differences between cell culture media

• Variations in incubation times and treatment responses

• Seeding densities across multiple time points

• Chemotherapeutic agents, and vehicle controls

The personalized support from their bioinformatics team for novel targets and biomarkers help you with obtaining:

• Dose-response curve graphs

• Combination index graphs

• Inhibition heat maps for concentration combinations

• 2D contour maps

• 3D response surface plots

• Guided analysis and reporting

In addition to the unique features offered by this technology, you can also monitor the incoming data real-time via secure online client accounts.

This screening runs every 3 months and internal drug controls and cell line revival costs are covered by Crown Bioscience ensuring a substantial amount of cost cutting.

To increase the efficiency of the outcome, OmniScreen™ keeps historical data from over 100 studies. You can make informed predictions on cell line growth parameters and responses to specific drug candidates based on how specific cell lines previously responded to drug candidates. This gives you an opportunity to maintain clear relevance to in vivo models and real-life clinical settings.

OmniScreen™ is an excellent solution to assess the early efficacy and potency of oncology drug candidates by running initial screens with large-scale cancer cell line panels, saving both time and costs. With its unique features, customized panels, and personalized support, it is the best shot for clients to achieve their desired results.

*GVRP is the authorized distributor of Crown Bioscience services in India. Contact us for more information on how to get started with OmniScreen™ for your projects.

Written by: Supriya Avatapalli
Sai Supriya has a 2 year experience in academic research and fair exposure to transition into industry. She enjoys delving deep into the new developments in the biotech, pharma industry and collaborating with people. She is zealous and keen to direct her best strengths to the role by being receptive to new ideas and challenges.

Testing the biological activity of pharmaceutical drugs, agro-chemicals and other xenobiotics on human relevant systems has increasingly become an important regulatory requirement to make a go or no-go decision (drug selection and risk assessment) before proceeding to a clinical trial.

In an API industry, out of the 100% compounds that reach the pre-clinical stage, only 3-5% reach the phase 1 of clinical trials¹. At pre-clinical stage the number of compounds drastically reduces from 10,000-20,000 to 20. Therefore, identifying a safe, potent, and efficacious drug requires thorough pre-clinical testing, which evaluates aspects of pharmacodynamics, pharmacokinetics, and toxicology in in-vitro and in-vivo setting².

In the R&D department of drug discovery, judicious use of time and costs is of utmost importance given the low chances of arriving at a candidate molecule which can potentially enter human clinical trials. Keeping this in mind, it is a wise choice to start by filtering out the leads using simpler and ethically less-critical methods to proceed towards the pipeline.

In-vitro testing is one such ethically less-critical approach towards filtering out the leads which produces dependable results in a short span of time. It allows screening of multiple compounds in a short span of time. The recent progress in this space makes in-vitro testing a lucrative strategy to start the pre-clinical testing with the use of – Stem cells – Embryonic & adult stem cells, and Induced Pluripotent stem cells (iPSCs), 3D Tissue models, Organ-on-chip systems and multi-organ-chip, In-silico models, and Spheroids and Organoids.

Our partner Crown Bioscience, Inc. has developed their proprietary database, OrganoidBase^TM featuring the PDX-derived organoid (PDXO) tumour models and patient derived organoids (PDO) to improve predictivity. Crown Bioscience, Inc. created a suite of powerful 3D in-vitro imaging-based assays that recapitulate and quantify complex human biology in a robust and high-throughput imaging platform.

Though the advancements in in-vitro testing systems is intriguing and laudable, a void in monitoring the exact performance of a drug in micro-environment of an organ is a miss³. Fortuitously, we have the in-vivo testing approach to verify the results obtained from in-vitro or in-silico. In-vivo preclinical studies using research models like mice, rats, guinea pigs, rabbits etc., enable the researchers get one-step closer to the candidate molecule/ drug. The appropriate cellular and physiological conditions of a whole organism in research models⁴, make the results obtained from in-vivo testing validate the in-vitro studies performed and confidence to continue with clinical trials.

The complete visible effect of a compound/ product on a living organism like interactions, metabolism, and distribution via in-vivo testing⁵ can help researchers make informed decisions.

However, the traditional in-vivo testing systems though reliable, lack the ability to precisely replicate the interaction of the compounds with human tissues³ – a major obstacle that demands an advancement in the in-vivo testing space. To overcome this obstacle in in-vivo testing, our partner and global leader in research model breeding and distribution, Envigo RMS LLC, came up with Humanized genetically engineered mice models (hGEMMs) that can help study the interaction between human tissues and tumour cells. Some popular humanized research models available with Envigo RMS LLC include: hACE2 knockin mice & rats, hACE2/hTmprss2 double knockin mice, hTmprss2 knockin mice. The research use and application of these research models includes oncology, cardiovascular, infectious diseases, and COVID-19.

Stephen Covey’s advice from one of his bestsellers – “Begin with the end in mind” is also applicable to drug development. The goal in drug development is to successfully file an IND/NDA and its prescribed use in the clinic⁶. Considering how the benefits of in-vivo testing fills the gaps in in-vitro testing and vice-versa, it is a smart choice to recognize the vantage point of balance between the two testing types and advance your research.

References:

1. Ranjita Shegokar, Chapter 2 – Preclinical testing—Understanding the basics first, Editor(s): Ranjita Shegokar, Drug Delivery Aspects, Elsevier, 2020, Pages 19-32, ISBN 9780128212226, https://www.sciencedirect.com/science/article/abs/pii/B9780128212226000026
2. Honek, J. (2017). Preclinical research in drug development. Medical Writing, 26, 5-8.
3. Yin L, Wang XJ, Chen DX, Liu XN, Wang XJ. Humanized mouse model: a review on preclinical applications for cancer immunotherapy. Am J Cancer Res. 2020 Dec 1;10(12):4568-4584. PMID: 33415020; PMCID: PMC7783739.
4. Tian H, Lyu Y, Yang Y-G and Hu Z (2020) Humanized Rodent Models for Cancer Research. Front. Oncol. 10:1696. doi: 10.3389/fonc.2020.01696
5. https://www.zeclinics.com/blog/differences-between-in-vitro-in-vivo-and-in-silico-assays-in-preclinical-research/
6. Steinmetz, K.L., Spack, E.G. The basics of preclinical drug development for neurodegenerative disease indications. BMC Neurol 9 (Suppl 1), S2 (2009). https://doi.org/10.1186/1471-2377-9-S1-S2

Written by: Sai Supriya
Sai Supriya has a 2 year experience in academic research and fair exposure to transition into industry. She enjoys delving deep into the new developments in the biotech, pharma industry and collaborating with people. She is zealous and keen to direct her best strengths to the role by being receptive to new ideas and challenges.