An Introduction to Transfection, Transfection Protocol and Applications – Technology Networks

The ability to alter the genetic composition of living cells has revolutionized biology. Scientific advances, from treating genetic disorders through gene therapy to reprograming skin cells into neurons, have been made possible by the increasing proficiency in introducing foreign nucleic acids (DNA and RNA) into cells using a technique known as transfection.

In 1928, Griffith proposed the transforming principle having observed that bacterial cells could take up foreign hereditary genetic material.1 This led to the discovery of DNA as that genetic material,2 a discovery that enabled great strides in science. In the 1960s, viruses were employed to transfer genetic material into animal cells in a controlled manner and it was shown that foreign genetic material could be expressed in animal cells; this opened up the possibility of gene therapy.3 The simultaneous advances in the field of recombinant technology the discovery of plasmids4 followed by an increased application of plasmids in the 1970s and the discovery of restriction enzymes5,6 facilitated the manipulation of genes. Around the same time, chemical and physical methods of introducing the genetic material into cells, such as electroporation,7 calcium phosphate transfection8 and liposomal9 transfection were also developed, thus providing a plethora of methods to deliver the modified genes into cells of interest.

With the development of transfection methods, many discoveries in basic and translational sciences have been possible and the technique has a plethora of applications in biology. This includes understanding the role of target genes in healthy and diseased cells, unraveling molecular pathways, designing gene therapeutic approaches, cellular reprograming and many more. Thus, transfection is now an indispensable molecular and cell biology laboratory technique. In this article, we discuss the fundamentals of transfection and provide an overview of some of the commonly employed methods. A sample protocol that can be used as a starting point is included and finally, we consider some of the key applications of transfection.

Transfection is a commonly used technique employed to transfer foreign nucleic acids into eukaryotic cells.10 The purpose of transfection is to alter the genetic content of the host cells, thus changing the expression of desired genes in these cells.

It is important here to distinguish between the terms transfection and transformation. While the term transfection is used when the host cells are eukaryotic, the term transformation is used to denote the transfer of nucleic acids to bacterial cells. This distinction is vital because in higher eukaryotic cells, transformation refers to the process by which the cells become malignant.11

The primary objective of a transfection technique is to ensure that the desired foreign nucleic acid can cross the cell membrane and that a substantial amount of that nucleic acid is protected from degradation to allow its expression within the cell. The transfer of nucleic acids into host cells can be achieved through various physical, chemical and biological methods. In most of these cases, the cellular uptake of the nucleic acids is mediated through endocytosis12 of the nucleic acid along with a carrier (Figure 1). A portion of these nucleic acids can avoid lysosomal degradation through what is known as endosomal escape and make their way to the nucleus where they can be transcribed to affect gene expression. While this is not an exhaustive list of the methodologies employed to achieve transfection, we summarize here some of the most commonly used transfection methods.

Figure 1:Diagrammatic representation of the generalized mechanism of transfection.

Physical methods of transfection apply electrical, mechanical or thermal forces13 to facilitate nucleic acid entry into host cells. Some examples include microinjection, electroporation, biolistic transfection (gene gun), sonoporation, magnetofection and laser optoporation. While the microinjection method employs a special needle to inject the nucleic acids directly into the cells, the other physical methods involve inducing transient and reversible permeabilization of the cell membrane while simultaneously placing the nucleic acids in the vicinity of the permeabilized membrane.14 In electroporation, short and intense electrical pulses are applied to achieve transient permeabilization of the cell membrane. Similarly, ultrasound waves achieve transient cell membrane permeabilization in the case of sonoporation; and the same effect is achieved using controlled exposure to a laser beam in the case of laser optoporation. Biolistic approaches propel naked DNA coated with heavy metal particles into the cell using gas discharge. Magnetofection utilizes magnetic nanoparticles to guide the nucleic acids to the cell membrane where they can be taken up by the process of endocytosis. Physical methods of transfection have the advantage that they do not pose an immunogenic risk like viral methods and are not restricted in the length of the nucleic acid sequences that can be used like viral and some chemical methods. However, these methods require dedicated and expensive equipment and reagents, and they often offer low transfection efficiencies with high cellular mortality.

A number of chemical reagents have been developed to assist DNA/RNA to cross the cell membrane.15 These include cationic lipids, calcium phosphate, cationic polymers and nanoparticles. Transfection using cationic liposomal lipids is termed as lipofection and involves the formation of positively charged lipid aggregates surrounding the negatively charged nucleic acid molecules that can easily merge with the bilipid cell membrane and enter the host cell. Positively charged calcium phosphate molecules form a complex with the negatively charged nucleic acid molecules and generate a precipitate that enters the host cells through endocytosis. The calcium phosphate method of transfection does not require special reagents and is inexpensive. However, this method has limited reproducibility with low transfection efficiency that depends on the cell type. Cationic polymers, such as dendrimers, linear or branched poly (ethylene imine) (PEI), poly (L-lysine) and others are examples of cationic polymers. Several polymeric nanoparticles, solid lipid nanoparticles (SLNP) and inorganic nanoparticles have been used for chemical transfection.12

Viral vectors of transfection offer the highest efficiency and can transfect a large variety of cell types. Virus-mediated biological transfection is termed transduction. Although the term transfection is sometimes used when nucleic acid delivery into host cells is achieved using viral particles, transduction is the correct term that should be used to refer to this process of viral-mediated delivery. Adenoviruses, adeno-associated viruses and retroviruses have been developed for transduction.16 Adenoviruses are double-stranded DNA viruses that can be used to transduce both dividing and non-dividing cells for a short duration. They can elicit strong host immune responses and the experiments with adenoviruses need to be performed in biosafety level 2 laboratories. Adeno-associated viruses (AAV) are single-stranded DNA viruses with an inability to replicate. They induce a weaker immune response in host cells. Retroviruses are RNA viruses that are characterized by the integration of their RNA into the host genome after reverse transcription. This leads to prolonged expression of the gene of interest. Lentiviruses, gammaretroviruses, spumaviruses and alphateroviruses are examples of retroviruses that have been used for biological transfection.12

Whats the difference between stable transfection and transient transfection?

Transfection can be classified as stable or transient (Figure 2) depending on the duration of retention of the genetic material in the host cells.17 If the transfected nucleic acids are incorporated into the host DNA or are retained in the host nucleus as an extrachromosomal element, leading to a permanent change in the expression of the desired gene, the process is termed stable transfection. Stable transfection facilitates constitutive expression of genetic material in cell lines and is useful for the generation of clonal cell lines, large-scale protein production applications and also for stable expression during gene therapy.

Transient transfection, on the other hand, does not involve the incorporation of the foreign nucleic acid into the host cell genome, resulting in short-term expression of the target genetic material. The nucleic acids are often removed from the cell as a result of environmental perturbation or cell division. Transient transfection is often used to understand the temporary effect of the change in expression on the desired cellular processes.

Here, we describe a generalized lipofection protocol18 for adherent secondary cell lines and primary cell cultures with plasmid DNA (Figure 3). The quantities of the plasmid DNA and reagents used are applicable for a single well of a 6-well plate and will have to be scaled depending on the size of the culture dish. Lipofection is a relatively low cost, safe, easy and quick method of transfecting cells. While this protocol can be a good starting point, the parameters will have to be standardized and optimized based on the properties of the DNA/RNA as well the host cell type. All procedures are performed under sterile conditions.

A) Before transfection:

Plasmid DNA: The quality of plasmid DNA is very important for efficient transfection. The gene of interest is usually cloned into an appropriate plasmid DNA backbone downstream from a suitable promoter. A pure and concentrated plasmid DNA preparation is required for transfection.

Plating of cells: The host cells are trypsinized, counted and plated onto an appropriate culture dish in complete culture media 1824 h before transfection. The cell numbers need to be adjusted so that they reach a confluency of 5075% at the time of transfection. Care must be taken to avoid contamination and maintain optimal cell health.

B) Transfection:

C) Post-transfection:

The transfection mix is replaced with 3 mL of complete culture media in each well. The cells are incubated for at least 48 h at 37 in the 5% CO2 incubator. The health of the cells should be monitored regularly.

We have previously described the biological methods of transfection that employ viruses for the delivery of nucleic acids. The term transduction is often used to describe virus-mediated delivery of nucleic acids into host cells. Bacteriophages were first shown to transduce bacterial cells in 1952.19 Since then, viral vectors have been developed to deliver genetic material into host cells by exploiting the natural propensity of certain viruses to transduce cells. Table 1 summarizes the differences between non-viral transfection and transduction.

Table 1: Comparison of transfection and transduction.

Transfection

Transduction

Delivery of foreign nucleic acids using non-viral methods

Delivery of foreign nucleic acids using viral vectors

Gene-transfer efficiency depends on the type of cells, media conditions etc. and is relatively low

Greater gene transfer efficiency

Serum in the media interferes with cellular uptake of nucleic acids

Transduction can be performed in the presence of serum

These methods are relatively harmless to the lab personnel

Viral contamination needs to be carefully handled. Appropriate biosafety measures should be practiced

Often requires specialized equipment and/or special reagents

Relatively easy to perform

Some methods and reagents can be cytotoxic

Viral infection of cells may induce cytopathic effects, such as insertional mutagenesis and immunogenicity

Physical methods, such as electroporation, gene gun and microinjection, and chemical methods, such as lipofection and calcium phosphate transfection, are examples of transfection

Viral transduction is mediated by DNA viruses, such as adenovirus and adeno-associated virus and RNA viruses, such as lentiviruses

Transfection methods have a wide range of applications. Here, a few of them have been briefly described.

Gene therapy: Gene therapy refers to treating genetic diseases by either silencing a defective gene, replacing a defective gene with the corrected version or amplifying the expression of a gene. Over the years, gene therapy has been used to treat diseases such as sickle cell anemia, beta thalassemia, Duchennes muscular dystrophy and hemophilia.20

DNA vaccines: DNA vaccines are vaccines that transfect host cells with engineered DNA plasmids to facilitate the expression of recombinant antigens in vivo.21 These antigens are recognized by the hosts body and stimulate the generation of adaptive immunity. The entry of DNA plasmids into host cells is achieved through in vivo electroporation.

Gene silencing: Transfection of cells with RNA interference (RNAi) molecules such as small interfering RNA (siRNA), which disintegrate the mRNA, or micro-RNA (miRNA), which suppress the translation of the gene of interest, leads to gene knockdown. Gene silencing can also be achieved using the CRISPR/Cas9 system.

Stable cell line generation: Stable transfection is used to generate stable cell lines that express a recombinant protein constitutively. These stable cell lines are extremely useful for large scale production of recombinant proteins. Stable cell lines that express recombinant proteins or have gene knock in/down are often used to study cellular processes and understand the structures of proteins22 in laboratories.

Virus production: Viral vectors for applications such as gene therapy involve the insertion of the desired gene into the viral plasmid backbone. The plasmids encoding the different components of the viral vector are transfected into a secondary cell line for assembly and large-scale production of the viruses. Moreover, viral production is employed for the generation of recombinant viruses such as, the influenza A virus, to study the effects of novel mutations and viral strains on the ability of the virus to infect and the efficiency of vaccines.23

Large-scale protein production: Recombinant proteins have many applications in therapeutics and several monoclonal antibodies, hormones, enzymes and clotting factors are produced as recombinant proteins on an industrial scale.24 Further, the rapidly progressing field of precision cellular agriculture, which is a sustainable alternative to traditional agriculture, employs transfection as an important step to enable lab-based production of future foods such as, milk, eggs and plant hemoglobin.25 Large-scale production of recombinant proteins has been achieved through transfection of recombinant DNA into mammalian cells, bacteria, yeast, plant and insect cells.

Stem cell reprograming and differentiation: Somatic cells can be reprogramed into induced pluripotent stem cells (iPSCs), which can be differentiated into specific cell types by inducing the expression of certain transcription factors. The development of iPSC technology has been possible thanks to the ability to transfect the genes required for reprograming and differentiation of the stem cells. This technology has led to the development of cellular models of human diseases and has immense therapeutic potential.26,27

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Clonal architecture evolution in Myeloproliferative Neoplasms: from ... - Nature.com

Autism Therapy Market Anticipated to Garner Significant Growth of … – GlobeNewswire

MELBOURNE, April 04, 2023 (GLOBE NEWSWIRE) -- Data Bridge Market Research completed a qualitative study titled "Autism Therapy Market" with 100+ market data tables, pie charts, graphs, and figures spread across Pages and an easy to grasp full analysis. A steadfast Autism Therapy market research report serves to be a very momentous component of business strategy. This report provides important information which assists to identify and analyze the needs of the market, the market size, and the competition with respect to Autism Therapy industry. When the market report is accompanied with precise tools and technology, it helps tackle a number of uncertain challenges for the business. This market research report is one of the key factors used in maintaining competitiveness over competitors. Autism Therapy market report supports the business to take better decisions for the successful future planning in terms of current and future trends in particular product or the industry.

Data Bridge Market Research analyses that the autism therapy market, which was USD 2.05 billion in 2022, would rise to USD 3.42 billion by 2030 and is expected to undergo a CAGR of 6.60% during the forecast period 2023 to 2030. In addition to the insights on market scenarios such as market value, growth rate, segmentation, geographical coverage, and major players, the market reports curated by the Data Bridge Market Research also include depth expert analysis, patient epidemiology, pipeline analysis, pricing analysis, and regulatory framework.

Download a PDF Sample of the Autism Therapy Market @https://www.databridgemarketresearch.com/request-a-sample/?dbmr=global-autism-therapy-market

Autism therapies are the type of therapies that are applied in autistic children or adults to improve or enhance their condition. Different therapies include speech-language therapy, behavior therapy, play-based therapy, occupational therapy, physical therapy, and nutritional therapy. This neurological disorder is related to several disabilities, such as challenges with the individual's behavior or lack of social skills. The diagnosis of autism can be made from a very early age, but the cause is still unknown.

The growing incidence of autism and pervasive developmental disorder (PDD) is essential to escalate market growth. Huge research studies performed by organizations to assess the safety and efficiency of drugs in patients with ASD are anticipated to boost market growth. The stimulants segment dominated the market with a huge revenue share due to the wide availability and ease of accessibility of drugs to patients.

Fundamental Aim of Autism Therapy Market Report

In the Autism Therapy market, every company has goals, but this report focus in on the most important ones, allowing you to gain insight into the competition, the future of the market, potential new products, and other useful information that can boost your sales significantly.

Some of the major players operating in the autism therapy market are:

Recent Development

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The investment made in the study would provide you access to information such as:

Opportunities:

The increasing demand for stimulants is boosting the growth of the market. Adderall, Focalin, Vyvanse, Dexedrine, and Ritalin are some stimulants approved by the U.S. FDA for treating patients who have autism. These drugs improve patient behavior by 80% when administered properly to patients. Therefore, growing efficiency related to the stimulants may attract a new target population and boost market growth.

A growing number of product launches associated with autism therapy boost market growth. For instance, the FDA granted fast-track designation to Curemark's CM-AT specified for ASD in 3-8 years old children in 2022. Furthermore, Indian researchers developed the 6BIO compound in 2021, which has shown the potential to enhance daily activities in the pre-clinical investigation of patients with an autism spectrum disorder. Thus, this factor boosts market growth.

Key Growth Drivers:

The increasing incidence of the autistic population is boosting the market's growth. For instance, France and Portugal have the lowest rates of autism in the world, with approximately 0.69% and 0.71%, respectively, as per the research published by Health Data Exchange. In 2021, the CDC stated that nearly 1 in 44 children in the U.S. is diagnosed with an autism spectrum disorder (ASD). Thus, this increasing prevalence demands high adoption of therapies, boosting the market growth.

Huge research studies performed by organizations to assess the safety and efficacy of drugs in patients with ASD are anticipated to drive the market. The positive outcomes of these studies lead to new growth opportunities for the market. For instance, Stalicla completed phase 1b trials of precision medicine candidate STP1 and witnessed positive results with symptom improvement in patients with ASD in 2022. Therefore, the effective completion of the trial and following product approvals are estimated to drive the market. Thus, this factor boosts market growth.

Read the In-Depth Research Report @https://www.databridgemarketresearch.com/reports/global-autism-therapy-market

Key Market Segments Covered in Autism Therapy Industry Research

Age Group

Type

Treatment Type

Drug

Distribution Channel

Autism Therapy Market Regional Analysis/Insights:

The countries covered in the autism therapy market report are U.S., Canada, and Mexico in North America, Germany, France, U.K., Netherlands, Switzerland, Belgium, Russia, Italy, Spain, Turkey, Rest of Europe in Europe, China, Japan, India, South Korea, Singapore, Malaysia, Australia, Thailand, Indonesia, Philippines, Rest of Asia-Pacific (APAC) in the Asia-Pacific (APAC), Saudi Arabia, U.A.E, South Africa, Egypt, Israel, Rest of Middle East and Africa (MEA) as a part of Middle East and Africa (MEA), Brazil, Argentina and Rest of South America as part of South America

North America dominates the autism therapy market due to increasing R&D activities and the launching several new products through mergers and strategic partnerships in this region. Also, the increasing awareness about the availability of numerous therapies to treat patients with autism spectrum disorders in this region

Asia-Pacific is expected to witness significant growth due to the wide presence of major market players and strategic initiatives undertaken by them to develop and commercialize several new products to treat patients.For instance, Teijin Pharma and Hamamatsu Medical University confirmed the safety, efficiency, and tolerability of oxytocin nasal spray for treating patients with an autism spectrum disorder in 2022

Table of Contents:

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Autism Therapy Market Anticipated to Garner Significant Growth of ... - GlobeNewswire

10th International Multithematic Scientific Bio-Medical Congress … – Nature.com

The 10th International Multithematic Bio-Medical Congress (IMBMC) 2022, Bio-Medical Scientific Cyprus, took place at European University Cyprus (EUC), Nicosia, Cyprus, under the auspices of the Ministry of Health and the Cyprus Medical Association. IMBMC is an internationally recognized event that was founded and established by Professor Dr Ioannis Patrikios, the Deputy Dean and Faculty member of the School of Medicine at EUC. During the 10th IMBMC, both Sir Gregory Winter (Nobel Prize in Chemistry, 2018, on protein and antibody engineering and antibody therapies) and Sir Martin Evans (awarded the 2007 Nobel Prize in Physiology or Medicine for his groundbreaking discoveries on embryonic stem cells and DNA recombination in mammals) were announced as Honorary Professors of the School of Medicine, European University Cyprus.

The first honorary keynote speaker Professor Sir Gregory Winters contribution engaged in the science of protein engineering. Being the founder of both Cambridge Antibody Technology (1989) and Domantis (2000), he spearheaded the use of a new class of drugs using engineered antibody technology to treat pathological diseases. At the Laboratory of Molecular Biology, Dr Winter focused on innovating techniques to familiarize the use of antibodies in the field of therapeutics, with his goal being to develop entirely humanized antibodies, using combinational gene repertoires. Over half of the antibodies sold today are a result of his inventions, including the humanized antibodies Campath-1H, Herceptin, Avastin, Synagis, and the first human antibody (Humira) to receive approval by the US Food and Drug Administration. Precisely, antibodies, as todays principal biological drug, especially for the treatment of cancer and autoimmune diseases, have replaced areas that were poorly served by chemical drugs. Will such developments thrive.

Professor Dr Kypros Herodotou Nicolaides spoke on preeclampsia (PE), which is a leading cause of maternal mortality and severe morbidity, in association with increased perinatal risks. He focused on ways to approach PE. These included actions on specific weeks and interventions to tackle PE, the rate, and the rate of term. Three methods were used. The first method to target PE was aspirin (150mg per day from 12 to 36 weeks reduced the rate of PE <32 weeks by 90%, PE <37 weeks by 60%), which had no effect on term PE. The second one included the incorporation of maternal characteristics in blood pressure, serum placental growth factor, and serum sFlt-1, which identified about 70% of women who developed term PE. Unfortunately, it was found that the use of pravastatin did not reduce the rate of term PE. The last approach to prevent term PE involved screening at 36 weeks with planned delivery at 37, 38, 39, and 40 weeks, respectively. This method was considered to reduce the rate of PE by more than 50%.

Professor Dr Gregg L. Semenza gave a speech that featured his lab discovery of hypoxia-inducible factor 1 (HIF-1). As he mentioned, a continuous supply of oxygen is necessary for each of the fifty trillion cells in the adult human body. HIF regulates thousands of genes according to oxygen availability, a discovery that awarded him with the 2019 Nobel Prize in Physiology or Medicine. The aim targeted the inhibition of cancer progression, relying on the molecular mechanisms of oxygen homeostasis, in association with HIF-1. It was intended to develop HIF inhibitors that could treat cancer and blinding eye diseases.

Professor Dr Stylianos E. Antonarakis presented two research themes, the former entitled Human Genomes and the Evolution of Medicine and the latter How to make an external ear: the story of FOXI3. The first study focused on the human genome sequence and variation as a fundamental component in health and disease. He stated the importance and impact of genomic variation on phenotypic variation and the evolving knowledge of individual genomic variation; the practice of medicine is gradually evolving. Diagnosis, prevention, and therapy are all evolving as the mysteries of the genome are elucidated. Genomic Medicine takes the spotlight regarding the etiology of the myriad of constitutional and somatic disorders and raises expectations for the development of rationalistic and intelligent therapeutic methods. His second speech focused on the developmental disorder craniofacial microsomia (CFM), which has a variety of manifestations, including external ear deformity. The CFM inheritance structure is obscure and debatable. The researchers identified pathogenic variants in the transcription factor FOXI3 that cause one form of CFM. Observations in human and mouse studies point to a recessive mode of inheritance in which the phenotypic diversity is caused by a fusion of rare (causative) and common (modifier) FOXI3 alleles. His studies pertain to the relationship between genomic variability and phenotypic variation that he has studied throughout his life.

Professor Dr Philippe Menasch, a cardiac surgeon, gave a presentation entitled Cells for Heart Failure: Replacement Therapy or Paracrine Signaling? He noticed the benefit in terms of function even though the cells were no longer physically present in the transplanted tissue, which prompted a change from the original idea of replacement therapy to paracrine signaling, in which the combination of biomolecules secreted by the cells and primarily gathered in extracellular vesicles (EV) harness endogenous repair pathways. Despite the issues presented in the field, biodistribution and fate-tracking studies suggest that intravenously delivered cells or their secreted products are trapped in remote organs with very limited cardiac homing even though using EV from cardiac-committed cells may improve their targeting at same-tissue recipient cells. The bridge between this remote sequestration and a cardiac benefit might be a shift of the phenotype of locally present endogenous immune cells toward a reparative pattern. Thereby making these cells the conveyors of the cell- or secretome-induced protective effects. Thus, while the initial hypothesis underlying the use of cells for treating heart failure was that they could act as a replacement therapy, the current trend is to rather consider them as inducers of paracrine signaling. In the case of heart failure, but also for other conditions, the major effect of this signaling seems to be a modulation of systemic inflammation whose benefits then translate at the level of the diseased organ. More recently, the group has refocused its interest toward leveraging the paracrine effect of cells to generate a cellular secretome, which might help streamline clinical applications.

Professor Dr Paul Moss, who specializes in the field of hematology, presented: From Diagnostics to Therapeutics; Antibodies Take Centre Stage in COVID-19, focusing on the worldwide increase in mortality rates due to COVID-19. He highlighted that both innate and adaptive immune systems provide partial protection against reinfection of the disease. Spike-specific antibodies are the major correlate of protection following vaccination, and individual responses depend on a range of factors such as age, gender, and comorbidity as specifically heighted. Considering that the coronavirus distinguishes among other infections, as the biological basis is unclear and further studies should be conducted around memory B cells and plasma cells, antibodies have also emerged as powerful therapeutic agents. Hence, antibodies have been the spotlight in the control, prevention, and policy management of the COVID-19 pandemic. The information that has been derived from this challenge can now be applied effectively to a range of other medical conditions.

Professor Dr Nikolai N. Korpan specializes in cryosurgery, which is defined as clinical implications that are used at extremely low temperatures, including an organ preservation technique. He presented his unique longstanding clinical experiences with ultra-low temperatures in treating patients with severe primary and secondary malignant diseases worldwide. Ice crystallization processes are of high importance, which damage the protein denaturation and rupture the cell membranes by the action of subzero cold in intracellular ice formation. This anti-cancer concept includes radical and palliative cryosurgical operations. Cryosurgical palliative methods with a pain reduction (painlessness or pain reduction) and fetor ex ore as well as improvement of the general state by getting the tumor under control are to achieve the major subjective facilitation with cancer patients, as he noted. Hence, in the near future, a new norm for oncological diagnosis and surgery will set a new bar for modern science and modern medicine. These theoretical stages will soon become a reality in medical practice according to his personal estimation.

Professor Dr Paolo Madeddu discussed the topic entitled Using Pericytes to Mend Broken Hearts: Where do we Stand? Pericytes were first found in the nineteenth century by Rouget. These cells surround capillaries in every organ of the human body, and he indicated the possible use of pericytes as a novel therapeutic avenue in regenerative medicine. He emphasized that pericytes are tissue-specific, multi-functional cells that are capable of treating vascular diseases. Dr Madeddus research activity examined the therapeutic effect of pericytes regarding ischemic heart disease, given the ability of pericytes to regenerate and repair heart tissue after myocardial infarction.

Professor Dr Amanda Varnava continued the session on The Ultimate Goal: Is Gene Therapy in Hypertrophic Cardiomyopathy Yet Possible? Dr Varnava has an interest in the cardiology of child-bearing period and runs a specialist pregnancy and heart disease service. Hypertrophic cardiomyopathy is the most prevalent congenital heart condition, affecting 1 in 500 of the population with devastating incidences of sudden cardiac death among young people. It is shown that the underlying genetic basis of the disease concerns gene mutation in the gene encoding of the cardiac sarcomere apparatus. A single change in the encoding system may lead to protein degradation and malfunction. Sequentially, sarcomeric dysfunction is inevitable as well as hypertrophy and myocardial fibrosis. Even though no therapeutic options are available to date, she discussed the importance of these molecular targets and suggested new targeted therapies to avoid complications and limit the mortality rate.

Professor Dr Gerasimos Filippatos gave a talk about Heart Failure Update. It was shown that sodium-glucose cotransporter 2 inhibitors, as drugs that improve the symptoms of heart failure and improves the left ventricular ejection fraction (LVEF). However, it remains unclear how these drugs benefit heart failure, as he clearly pointed out. Another second-line agent that was found to control heart failure outcomes is the oral soluble guanylate cyclase stimulator vericiguat, which is used for patients who have a reduced LVEF. Concerning inotropes, in patients who suffer from progressed heart failure with reduced ejection fraction, the myosin activator omecamtiv mecarbil can also improve HF outcomes again as he explained. Researchers have focused on the effect of diuretics, as when they are used in combination with other drugs, as they can improve both diuretic response and relieve congestion in hospitalized HF patients. Moreover, as he noted, diabetics and patients with chronic kidney diseases that are given non-steroidal mineralocorticoids in combination with spironolactone and eplerenone can have a positive effect on their cardiovascular and renal function. Prof. Filippatos concluded that in the field of ventricular assist devices, transdermal charging is the new frontier, as it eliminates the need for external leads providing a lower risk of infection and a better quality of life.

Professor Dr Vasso Apostolopoulos spoke on Vaccines in The New Era: What Have We Learnt in The Last 30 Years? Recently, her interest has shifted on how chronic diseases, such as cancer, autoimmune disorders, mental health, and infectious diseases, can be treated if approached from an immunologic perspective. The current research on checkpoint markers is shown to lead to apoptotic T cell behavior and immune escape mechanisms in the event of cancer. In the last 5 years, researchers have published numerous information about checkpoint markers as they relate to diseases such as autoimmune disorders, inflammatory disorders, and cancer. Peptide alterations of T cell epitopes with 12 amino acid mutations can control immune responses, by downregulating or upregulating feedback. The aim of her research is to reinforce innovative immune modulators/therapeutics/vaccines. Several innovative immune modulators against cancer, autoimmune disorders, and infectious diseases have been successfully established.

Professor Dr Kevin Harrington gave a speech entitled Is There a Rationale for Combining Radiotherapy and Immunotherapy in Patients with Head and Neck Cancer? Dr Harrington is a clinical oncologist who specializes in the development of novel treatments concerning head and neck cancer, for which he led multiple phase I, II, and III trials. In CheckMate-141 and KEYNOTE-040 and -048 studies, it was found that these agents, when combined with radiotherapy, are active regarding palliative treatment of relapsed and metastatic diseases. In preclinical studies, it was advised that ICPI therapy should be given simultaneously with RT. This suggestion was generalized into trial designs based on anti-PD1/-PD-L-1 therapy given 1 week before. The results of this study brought negative endpoints, similar to other studies, which also delivered negative outcomes at primary and secondary points, as he pointed out. The presentation greatly focused on the innovation of strategies to enhance the development of combination regimens for patients suffering from locally advanced head and neck cancers.

Ran Nir-Paz presentation entitled The Enemy of Your Enemy is Your Friend The Reintroduction of Bacteriophages for Resistant and Persistent Infections. His study focused on introducing phage therapy for resistant and persistent infections. Recently, the treatment method with bacteriophages for preserving infections has reappeared. The research involved a wide phage band with over 500 identified phages used to discover the most effective lytic phage and to develop treatment schemes. After supplying 15 Israeli patients with intravenous bacteriophages, it was found that 50% of the requests concerned respiratory, skin, and soft tissue infections. The clinical trials mentioned above were further analyzed in his lecture.

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10th International Multithematic Scientific Bio-Medical Congress ... - Nature.com