Genetically modified sperm

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Genetically modified sperm (GM sperm) is sperm that has undergone genetic modification for biomedical purposes, including the elimination of genetic diseases or infertility. [1] Although the procedure has been tested on animals such as fish, [2] pigs, [3] and rabbits, [4] it remains relatively untested on humans. [5] In the case of pigs, the goal of research is to inexpensively produce organs and supplement the shortage of donated human organs. [6] Although GM sperm has the potential to detect and treat genetic diseases, it will likely take many years for successful use in patients.

Contents

Process

In genetic modification, genes are inserted into living cells in order to change how proteins are created. A viral vector is often used to deliver the gene of interest to the chromosomes in the cell nucleus. Every daughter cell will reflect the genetic modification. [7]

Applications

GM sperm is not frequently used in humans but has been extensively tested and studied in animals. This type of modification of the sperm, eggs, or early embryos is known as an Inheritable Genetic Modification. Because the genetic changes are passed onto future generations, Inheritable Genetic Modification is far more consequential than somatic cell modifications. [8]

Regulations

Genetic modification of sperm cells, as a type of germline gene transfer, is subject to federal regulation in the United States under the Recombinant DNA Advisory Committee of the National Institutes of Health, as well as the Food and Drug Administration. [9] Regulation in the United States currently prohibits the application or research use of such technologies in humans, but does allow for research and commercial use, prior to approval, in animals. [10]

Controversy

Genetic modification in humans is a contested issue due to the variety of social and ethical issues it raises. One such controversy is the ability to modify the genes of future offspring to decrease the likelihood for certain diseases or modify the expression of chosen traits. [11] In a recent case, an American teenager successfully sued a sperm bank, because she had been born with fragile X syndrome. [12] Some also cite the promotion of eugenics through certain applications of genetic modification, justifying the moratorium on research and funding in human trials in many countries. [13]

Related Research Articles

Biotechnology Use of living systems and organisms to develop or make useful products

Biotechnology is a broad area of biology, involving the use of living systems and organisms to develop or make products. Depending on the tools and applications, it often overlaps with related scientific fields. In the late 20th and early 21st centuries, biotechnology has expanded to include new and diverse sciences, such as genomics, recombinant gene techniques, applied immunology, and development of pharmaceutical therapies and diagnostic tests. The term biotechnology was first used by Karl Ereky in 1919, meaning the production of products from raw materials with the aid of living organisms.

Genetically modified organism Organisms whose genetic material has been altered using genetic engineering methods

A genetically modified organism (GMO) is any organism whose genetic material has been altered using genetic engineering techniques. The exact definition of a genetically modified organism and what constitutes genetic engineering varies, with the most common being an organism altered in a way that "does not occur naturally by mating and/or natural recombination". A wide variety of organisms have been genetically modified (GM), from animals to plants and microorganisms. Genes have been transferred within the same species, across species, and even across kingdoms. New genes can be introduced, or endogenous genes can be enhanced, altered, or knocked out.

Genetic engineering Direct manipulation of an organisms genome using biotechnology

Genetic engineering, also called genetic modification or genetic manipulation, is the direct manipulation of an organism's genes using biotechnology. It is a set of technologies used to change the genetic makeup of cells, including the transfer of genes within and across species boundaries to produce improved or novel organisms. New DNA is obtained by either isolating and copying the genetic material of interest using recombinant DNA methods or by artificially synthesising the DNA. A construct is usually created and used to insert this DNA into the host organism. The first recombinant DNA molecule was made by Paul Berg in 1972 by combining DNA from the monkey virus SV40 with the lambda virus. As well as inserting genes, the process can be used to remove, or "knock out", genes. The new DNA can be inserted randomly, or targeted to a specific part of the genome.

Gene therapy Medical field

Gene therapy is a medical field which focuses on the genetic modification of cells to produce a therapeutic effect or the treatment of disease by repairing or reconstructing defective genetic material. The first attempt at modifying human DNA was performed in 1980 by Martin Cline, but the first successful nuclear gene transfer in humans, approved by the National Institutes of Health, was performed in May 1989. The first therapeutic use of gene transfer as well as the first direct insertion of human DNA into the nuclear genome was performed by French Anderson in a trial starting in September 1990. It is thought to be able to cure many genetic disorders or treat them over time.

Genetically modified food Foods produced from organisms that have had changes introduced into their DNA

Genetically modified foods, also known as genetically engineered foods, or bioengineered foods are foods produced from organisms that have had changes introduced into their DNA using the methods of genetic engineering. Genetic engineering techniques allow for the introduction of new traits as well as greater control over traits when compared to previous methods, such as selective breeding and mutation breeding.

Designer baby Genetically modified human embryo

A designer baby is a baby whose genetic makeup has been selected or altered, often to include a particular gene or to remove genes associated with a disease. This process usually involves analysing a wide range of human embryos to identify genes associated with particular diseases and characteristics, and selecting embryos that have the desired genetic makeup; a process known as preimplantation genetic diagnosis. Other potential methods by which a baby's genetic information can be altered involve directly editing the genome before birth. This process is not routinely performed and only one instance of this is known to have occurred as of 2019, where Chinese twins Lulu and Nana were edited as embryos, causing widespread criticism.

A transgene is a gene that has been transferred naturally, or by any of a number of genetic engineering techniques from one organism to another. The introduction of a transgene, in a process known as transgenesis, has the potential to change the phenotype of an organism. Transgene describes a segment of DNA containing a gene sequence that has been isolated from one organism and is introduced into a different organism. This non-native segment of DNA may either retain the ability to produce RNA or protein in the transgenic organism or alter the normal function of the transgenic organism's genetic code. In general, the DNA is incorporated into the organism's germ line. For example, in higher vertebrates this can be accomplished by injecting the foreign DNA into the nucleus of a fertilized ovum. This technique is routinely used to introduce human disease genes or other genes of interest into strains of laboratory mice to study the function or pathology involved with that particular gene.

The Center for Genetics and Society (CGS) is a nonprofit information and public affairs organization, based in Berkeley, California, United States. It encourages responsible use and regulation of new human genetic and reproductive technologies.

Ralph L. Brinster

Ralph Lawrence Brinster is an American geneticist, National Medal of Science laureate, and Richard King Mellon Professor of Reproductive Physiology at the School of Veterinary Medicine, University of Pennsylvania.

Genetically modified mouse

A genetically modified mouse or genetically engineered mouse model (GEMM) is a mouse that has had its genome altered through the use of genetic engineering techniques. Genetically modified mice are commonly used for research or as animal models of human diseases, and are also used for research on genes. Together with patient-derived xenografts (PDXs), GEMMs are the most common in vivo models in cancer research. Both approaches are considered complementary and may be used to recapitulate different aspects of disease. GEMMs are also of great interest for drug development, as they facilitate target validation and the study of response, resistance, toxicity and pharmacodynamics.

Plant genetics Study of genes and heredity in plants

Plant genetics is the study of genes, genetic variation, and heredity specifically in plants. It is generally considered a field of biology and botany, but intersects frequently with many other life sciences and is strongly linked with the study of information systems. Plant genetics is similar in many ways to animal genetics but differs in a few key areas.

Genetically modified animal

Genetically modified animals are animals that have been genetically modified for a variety of purposes including producing drugs, enhancing yields, increasing resistance to disease, etc. The vast majority of genetically modified animals are at the research stage while the number close to entering the market remains small.

Genetically modified fish

Genetically modified fish are organisms from the taxonomic clade which includes the classes Agnatha, Chondrichthyes and Osteichthyes whose genetic material (DNA) has been altered using genetic engineering techniques. In most cases, the aim is to introduce a new trait to the fish which does not occur naturally in the species, i.e. transgenesis.

Genetically modified virus Species of virus

A genetically modified virus is a virus that has been altered or generated using biotechnology methods, and remains capable of infection. Genetic modification involves the directed insertion, deletion, artificial synthesis or change of nucleotide bases in viral genomes. Genetically modified viruses are mostly generated by the insertion of foreign genes intro viral genomes for the purposes of biomedical, agricultural, bio-control, or technological objectives. The terms genetically modified virus and genetically engineered virus are used synonymously.

Regulation of genetic engineering Overview of the regulation of genetic engineering

The regulation of genetic engineering varies widely by country. Countries such as the United States, Canada, Lebanon and Egypt use substantial equivalence as the starting point when assessing safety, while many countries such as those in the European Union, Brazil and China authorize GMO cultivation on a case-by-case basis. Many countries allow the import of GM food with authorization, but either do not allow its cultivation or have provisions for cultivation, but no GM products are yet produced. Most countries that do not allow for GMO cultivation do permit research. Most (85%) of the world's GMO crops are grown in the Americas. One of the key issues concerning regulators is whether GM products should be labeled. Labeling of GMO products in the marketplace is required in 64 countries. Labeling can be mandatory up to a threshold GM content level or voluntary. A study investigating voluntary labeling in South Africa found that 31% of products labeled as GMO-free had a GM content above 1.0%. In Canada and the USA labeling of GM food is voluntary, while in Europe all food or feed which contains greater than 0.9% of approved GMOs must be labelled.

History of genetic engineering

Genetic engineering is the science of manipulating genetic material of an organism. The first artificial genetic modification accomplished using biotechnology was transgenesis, the process of transferring genes from one organism to another, first accomplished by Herbert Boyer and Stanley Cohen in 1973. It was the result of a series of advancements in techniques that allowed the direct modification of the genome. Important advances included the discovery of restriction enzymes and DNA ligases, the ability to design plasmids and technologies like polymerase chain reaction and sequencing. Transformation of the DNA into a host organism was accomplished with the invention of biolistics, Agrobacterium-mediated recombination and microinjection. The first genetically modified animal was a mouse created in 1974 by Rudolf Jaenisch. In 1976 the technology was commercialised, with the advent of genetically modified bacteria that produced somatostatin, followed by insulin in 1978. In 1983 an antibiotic resistant gene was inserted into tobacco, leading to the first genetically engineered plant. Advances followed that allowed scientists to manipulate and add genes to a variety of different organisms and induce a range of different effects. Plants were first commercialized with virus resistant tobacco released in China in 1992. The first genetically modified food was the Flavr Savr tomato marketed in 1994. By 2010, 29 countries had planted commercialized biotech crops. In 2000 a paper published in Science introduced golden rice, the first food developed with increased nutrient value.

Gene drive way to propagate genes throughout a population

A gene drive is a natural process and technology of genetic engineering that propagates a particular suite of genes throughout a population by altering the probability that a specific allele will be transmitted to offspring. Gene drives can arise through a variety of mechanisms. They have been proposed to provide an effective means of genetically modifying specific populations and entire species.

Human germline engineering is the process by which the genome of an individual is edited in such a way that the change is heritable. This is achieved through genetic alterations within the germ cells, or the reproductive cells, such as the egg and sperm. Human germline engineering is a type of genetic modification that directly manipulates the genome using molecular engineering techniques. Aside from germline engineering, genetic modification can be applied in another way, somatic genetic modification. Somatic gene modification consists of altering somatic cells, which are all cells in the body that are not involved in reproduction. While somatic gene therapy does change the genome of the targeted cells, these cells are not within the germline, so the alterations are not heritable and cannot be passed on to the next generation.

Horizontal Environmental Genetic Alteration Agents (HEGAAs) are any artificially developed agents that are engineered to edit the genome of eukaryotic species they infect when intentionally dispersed into the environment.

CRISPR gene editing Gene editing method

CRISPR gene editing is a genetic engineering technique in molecular biology by which the genomes of living organisms may be modified. It is based on a simplified version of the bacterial CRISPR-Cas9 antiviral defense system. By delivering the Cas9 nuclease complexed with a synthetic guide RNA (gRNA) into a cell, the cell's genome can be cut at a desired location, allowing existing genes to be removed and/or new ones added in vivo.

References

  1. "Animals From Genetically Modified Sperm". Archived from the original on 2012-07-23. Retrieved 2009-11-26.
  2. Genetically modified sperm in fish
  3. Manzini, S.; Vargiolu, A.; Stehle, I.; Bacci, M.; Cerrito, M.; Giovannoni, R.; Zannoni, A.; Bianco, M.; Forni, M.; Donini, P.; Papa, M.; Lipps, H. J.; Lavitrano, M. (2006). "Genetically modified pigs produced with a nonviral episomal vector". Proceedings of the National Academy of Sciences of the United States of America. 103 (47): 17672–17677. Bibcode:2006PNAS..10317672M. doi: 10.1073/pnas.0604938103 . PMC   1635978 . PMID   17101993.
  4. Wang, H. J.; Lin, A. X.; Zhang, Z. C.; Chen, Y. F. (2001). "Expression of porcine growth hormone gene in transgenic rabbits as reported by green fluorescent protein". Animal Biotechnology. 12 (2): 101–110. doi:10.1081/ABIO-100108336. PMID   11808625. S2CID   23132238.
  5. Scientists 'five years away' from creating human sperm and eggs in a laboratory
  6. "Human genes placed in pigs". The Cincinnati Post. 2002-10-22. Archived from the original on 2012-11-03. Retrieved 2010-02-08.
  7. "The Basic Science". Center for Genetics and Society.
  8. "Inheritable Genetic Modification". Center for Genetics and Society. Retrieved 11 April 2015.
  9. Hanna, Kathi. "Germline Gene Transfer". National Human Genome Research Institute. National Institutes of Health. Retrieved 10 April 2015.
  10. "Regulations of Genetically Engineered Animals". U.S. Food and Drug Administration. Food and Drug Administration. Retrieved 10 April 2015.
  11. Rasko, John; O'Sullivan, Gabrielle; Ankeny, Rachel (2006). The Ethics of Inheritable Genetic Modification - A Dividing Line?. Cambridge University Press. doi:10.1017/CBO9780511584275.003.
  12. "Sperm bank sued under product liability law". New Scientist . 2009-04-08. Retrieved 2010-02-08.
  13. Knapton, Sarah (June 2014). "Robert Winston: my research could open door to 'risky' eugenics". The Telegraph. Retrieved 11 April 2015.