Philip Felgner | |
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Born | Philip Louis Felgner 7 February 1950 Frankenmuth, Michigan, U.S. |
Alma mater | Michigan State University (B.S., M.S., Ph.D) |
Known for | Lipofection technologies |
Awards | Princess of Asturias Awards for Technical and Scientific Research (2021) Robert Koch Prize (2022) |
Scientific career | |
Fields | |
Institutions | University of California, Irvine |
Philip Louis Felgner (born 7 February 1950) is an American biochemist and immunologist, specialized in lipofection technology and genetics. [1] He is one of the developers of the vaccine against the SARS-CoV-2 virus, responsible for COVID-19 pandemic. He is currently the director of the UCI Vaccine Research & Development Center as well as the Protein Microarray Laboratory and Training Facility. [2]
In 1972, he graduated in biochemistry from the Michigan State University, earning his master's degree in 1975 and his Ph.D. in 1978. He did postdoctoral work at the University of Virginia. [3]
While working at Syntex in the mid-1980s, Felgner pioneered the use of artificially-created cationic lipids (positively-charged lipids) to bind lipids to nucleic acids in order to transfect the latter into cells. [4] Later while working at the Salk Institute for Biological Studies in San Diego, California, he performed experiments on the transfection of RNA into human, rat, mouse, Xenopus, and Drosophila cells, work which was published in 1989. [5] In 1990, while working at Vical, he collaborated with the University of Wisconsin, discovering that injection of pDNA and mRNA into mouse skeletal muscle resulted in high protein expression levels. [6] [7] These research are recognized as among the earliest steps towards mRNA vaccine development. [8]
In 2021, he was awarded the Princess of Asturias Awards for Technical and Scientific Research along Katalin Karikó, Drew Weissman, Uğur Şahin, Özlem Türeci, Derrick Rossi, and Sarah Gilbert. [9]
In 2022, Philip Felgner received the A.D. Bangham FRS Life Achievement Award, an award named in honor of Dr. Alec Douglas Bangham, known as the father of liposomes. [10]
In 2022, Philip Felgner was awarded the Robert Koch Prize, one of the stepping-stones to eventual Nobel Prize recognition for scientists in the fields of microbiology and immunology, for his fundamental contributions to the development of lipofection technology, a technology widely used in basic research in medicine for introducing active substances into cells and also the basis of modern mRNA vaccines. [11] [12]
In 2022, Philip Felgner was named Fellow by National Academy of Inventors. [13] As of 2022, he has published 280 papers that have been cited 44,000 times and has 53 U.S. patents and 56 foreign patents, including 14 licensed patents. [14]
In 2023, the pioneering work of synthesizing the first cationic lipid (DOTMA) (lipofectin) for DNA and RNA delivery into cells by Philip Felgner was mentioned in the advanced scientific information posted by the Nobel Prize committee for the Nobel Prize in Physiology or Medicine in 2023. [15] [16]
Small interfering RNA (siRNA), sometimes known as short interfering RNA or silencing RNA, is a class of double-stranded non-coding RNA molecules, typically 20–24 base pairs in length, similar to microRNA (miRNA), and operating within the RNA interference (RNAi) pathway. It interferes with the expression of specific genes with complementary nucleotide sequences by degrading messenger RNA (mRNA) after transcription, preventing translation. It was discovered in 1998 by Andrew Fire at the Carnegie Institution for Science in Washington, D.C. and Craig Mello at the University of Massachusetts in Worcester.
The Nirenberg and Matthaei experiment was a scientific experiment performed in May 1961 by Marshall W. Nirenberg and his post-doctoral fellow, J. Heinrich Matthaei, at the National Institutes of Health (NIH). The experiment deciphered the first of the 64 triplet codons in the genetic code by using nucleic acid homopolymers to translate specific amino acids.
Transfection is the process of deliberately introducing naked or purified nucleic acids into eukaryotic cells. It may also refer to other methods and cell types, although other terms are often preferred: "transformation" is typically used to describe non-viral DNA transfer in bacteria and non-animal eukaryotic cells, including plant cells. In animal cells, transfection is the preferred term as transformation is also used to refer to progression to a cancerous state (carcinogenesis) in these cells. Transduction is often used to describe virus-mediated gene transfer into prokaryotic cells.
A DNA construct is an artificially-designed segment of DNA borne on a vector that can be used to incorporate genetic material into a target tissue or cell. A DNA construct contains a DNA insert, called a transgene, delivered via a transformation vector which allows the insert sequence to be replicated and/or expressed in the target cell. This gene can be cloned from a naturally occurring gene, or synthetically constructed. The vector can be delivered using physical, chemical or viral methods. Typically, the vectors used in DNA constructs contain an origin of replication, a multiple cloning site, and a selectable marker. Certain vectors can carry additional regulatory elements based on the expression system involved.
Cationic liposomes are spherical structures that contain positively charged lipids. Cationic liposomes can vary in size between 40 nm and 500 nm, and they can either have one lipid bilayer (monolamellar) or multiple lipid bilayers (multilamellar). The positive charge of the phospholipids allows cationic liposomes to form complexes with negatively charged nucleic acids through ionic interactions. Upon interacting with nucleic acids, cationic liposomes form clusters of aggregated vesicles. These interactions allow cationic liposomes to condense and encapsulate various therapeutic and diagnostic agents in their aqueous compartment or in their lipid bilayer. These cationic liposome-nucleic acid complexes are also referred to as lipoplexes. Due to the overall positive charge of cationic liposomes, they interact with negatively charged cell membranes more readily than classic liposomes. This positive charge can also create some issues in vivo, such as binding to plasma proteins in the bloodstream, which leads to opsonization. These issues can be reduced by optimizing the physical and chemical properties of cationic liposomes through their lipid composition. Cationic liposomes are increasingly being researched for use as delivery vectors in gene therapy due to their capability to efficiently transfect cells. A common application for cationic liposomes is cancer drug delivery.
Lipofectamine or Lipofectamine 2000 is a common transfection reagent, produced and sold by Invitrogen, used in molecular and cellular biology. It is used to increase the transfection efficiency of RNA or plasmid DNA into in vitro cell cultures by lipofection. Lipofectamine contains lipid subunits that can form liposomes in an aqueous environment, which entrap the transfection payload, e.g. DNA plasmids.
Lipid-based nanoparticles are very small spherical particles composed of lipids. They are a novel pharmaceutical drug delivery system, and a novel pharmaceutical formulation. There are many subclasses of lipid-based nanoparticles such as: lipid nanoparticles (LNPs), solid lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs).
Sir Michael Houghton is a British scientist and Nobel Prize laureate. Along with Qui-Lim Choo, George Kuo and Daniel W. Bradley, he co-discovered Hepatitis C in 1989. He also co-discovered the Hepatitis D genome in 1986. The discovery of the Hepatitis C virus (HCV) led to the rapid development of diagnostic reagents to detect HCV in blood supplies, which has reduced the risk of acquiring HCV through blood transfusion from one in three to about one in two million. It is estimated that antibody testing has prevented at least 40,000 new infections per year in the US alone and many more worldwide.
Tasuku Honjo is a Japanese physician-scientist and immunologist. He won the 2018 Nobel Prize in Physiology or Medicine and is best known for his identification of programmed cell death protein 1 (PD-1). He is also known for his molecular identification of cytokines: IL-4 and IL-5, as well as the discovery of activation-induced cytidine deaminase (AID) that is essential for class switch recombination and somatic hypermutation.
Derrick J. Rossi, is a Canadian stem cell biologist and entrepreneur. He is a co-founder of the pharmaceutical company Moderna.
Dame Sarah Catherine Gilbert FRS is an English vaccinologist who is a Professor of Vaccinology at the University of Oxford and co-founder of Vaccitech. She specialises in the development of vaccines against influenza and emerging viral pathogens. She led the development and testing of the universal flu vaccine, which underwent clinical trials in 2011.
An mRNAvaccine is a type of vaccine that uses a copy of a molecule called messenger RNA (mRNA) to produce an immune response. The vaccine delivers molecules of antigen-encoding mRNA into cells, which use the designed mRNA as a blueprint to build foreign protein that would normally be produced by a pathogen or by a cancer cell. These protein molecules stimulate an adaptive immune response that teaches the body to identify and destroy the corresponding pathogen or cancer cells. The mRNA is delivered by a co-formulation of the RNA encapsulated in lipid nanoparticles that protect the RNA strands and help their absorption into the cells.
Katalin "Kati" Karikó is a Hungarian-American biochemist who specializes in ribonucleic acid (RNA)-mediated mechanisms, particularly in vitro-transcribed messenger RNA (mRNA) for protein replacement therapy. Karikó laid the scientific groundwork for mRNA vaccines, overcoming major obstacles and skepticism in the scientific community. Karikó received the Nobel Prize in Physiology or Medicine in 2023 for her work, along with American immunologist Drew Weissman.
Uğur Şahin is a German oncologist and immunologist. He is the co-founder and CEO of BioNTech, which developed one of the major vaccines against COVID-19. His main fields of research are cancer research and immunology.
Drew Weissman is an American physician and immunologist known for his contributions to RNA biology. Weissman is the inaugural Roberts Family Professor in Vaccine Research, director of the Penn Institute for RNA Innovation, and professor of medicine at the Perelman School of Medicine at the University of Pennsylvania (Penn).
SM-102 is a synthetic amino lipid which is used in combination with other lipids to form lipid nanoparticles. These are used for the delivery of mRNA-based vaccines, and in particular SM-102 forms part of the drug delivery system for the Moderna COVID-19 vaccine.
Robert Wallace Malone is an American physician and biochemist. His early work focused on mRNA technology, pharmaceuticals, and drug repurposing research. During the COVID-19 pandemic, Malone promoted misinformation about the safety and efficacy of COVID-19 vaccines.
A genetic vaccine is a vaccine that contains nucleic acids such as DNA or RNA that lead to protein biosynthesis of antigens within a cell. Genetic vaccines thus include DNA vaccines, RNA vaccines and viral vector vaccines.
Intracellular delivery is the process of introducing external materials into living cells. Materials that are delivered into cells include nucleic acids, proteins, peptides, impermeable small molecules, synthetic nanomaterials, organelles, and micron-scale tracers, devices and objects. Such molecules and materials can be used to investigate cellular behavior, engineer cell operations or correct a pathological function.