These breakthroughs demonstrate a sophisticated shift toward utilizing biological systems as scalable factories for addressing global medical scarcities. While the potential for insulin security and precision oncology is profound, the journey from experimental success to widespread clinical accessibility remains the critical hurdle.
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[music] >> Genetically modified cows that produce [music] insulin in their milk.
Genetically modified cows can produce proteins [music] in their milk needed to produce human insulin, scientists [music] have shown.
A new method of producing insulin could help [music] increase the global supply of the drug.
Insulin was discovered in 1921 [music] by Frederick Banting, who received the Nobel Prize for [music] it a few years later. [singing] This discovery was a breakthrough in the treatment [music] of diabetes.
Insulin is a hormone that regulates blood glucose [music] levels. Without it, blood glucose levels become too [music] high, which leads to diabetes and its numerous complications.
In 1955, [music] Frederick Sanger determined the amino acid sequence [music] of insulin, for which he was also awarded the Nobel Prize.
His [music] work allowed the synthesis of insulin.
Currently, insulin is produced by genetic [music] engineering using E. coli bacteria.
These bacteria are implanted with the gene responsible [music] for the production of human insulin and are the main source of medical insulin.
Similar [music] solutions were also introduced in the case of yeast. Before these techniques were developed, [music] diabetics took bovine insulin. Now scientists [music] from the University of Illinois and the Universidade de São [music] Paulo have developed a new way to produce insulin.
It [music] turns out that it can be produced by genetically modified cows in their [music] milk.
The study authors indicate that their method can eliminate [music] drug shortages and their high costs for people with diabetes.
The results [music] and description of the research were published in Biotechnology Journal.
The idea of using cows to produce insulin is not new, but only recent studies have confirmed that it can be done. The authors of the study believe that a herd of cattle modified in this way could compete with current methods of insulin production, [music] which are based on genetically modified yeast and bacteria. [music] Diabetes is a disease characterized by elevated blood glucose levels. [music] This is caused by a defect in the beta functioning of the beta cells of the pancreas, [music] which produce insulin to lower blood sugar levels.
In type 1 diabetes, beta [music] cells are destroyed by the immune system.
As a result, the ability to produce insulin disappears.
In type 2 diabetes, tissue [music] sensitivity to insulin is reduced. As a result, the body demands increased insulin production, which exceeds the capabilities of beta cells. As a result, beta cells do not function properly and the level of insulin in the body decreases, >> [music] >> although it is still produced.
Type 2 diabetes is the most common form of diabetes.
Scientists have been wondering for years how to help people with diabetes.
>> [music] >> In a 2020 study, they successfully tested a new technique on mice to transform human stem cells into insulin-producing [clears throat] beta cells of the pancreas.
The condition of rodents with acute diabetes that underwent therapy quickly improved.
>> [music] >> His blood glucose levels returned to normal and remained so for many months.
In turn, in research from a year ago, scientists reprogrammed stem [music] cells obtained from human stomach tissue into cells resembling insulin-secreting pancreatic cells, known as beta cells.
[music] Transplanting small groups of such cells reversed the symptoms of diabetes in mice.
Mother nature designed the mammary gland as a factory for really efficient protein production.
"We can use this system to produce protein that could help hundreds of millions of people around the world," said Matt Wheeler [music] from the University of Illinois, lead author of the paper.
As part of [music] the new study, scientists introduced a section of human DNA coding [music] for proinsulin, a protein that converts into insulin, into the cell nuclei of 10 cow embryos.
[music] The embryos were then placed in the wombs [music] of cows that had not undergone any modifications.
Of the 10 cows, [music] only one became pregnant and gave birth to a transgenic [music] calf.
Human DNA was targeted for expression, the process by which gene sequences are read and converted [music] into protein products, exclusively in breast tissue.
"In the old days, we just [music] threw in DNA and hoped it would be expressed where we wanted it.
Nowadays, [music] we can be much more strategic and intentional.
Using a DNA [music] construct specific to mammary tissue means that there is no human insulin circulating [music] in the cow's blood or other tissues.
It also [music] takes advantage of the mammary gland's ability to produce large amounts of protein," [music] Wheeler said.
Once the transgenic cow reached [music] sexual maturity, scientists attempted to impregnate it using [music] standard artificial insemination techniques. They tried in vitro [music] fertilization, artificial insemination, and even old-fashioned methods.
>> [music] >> However, none of them were successful.
Ultimately, they induced lactation in the cow through hormonal induction.
Lactation produced milk, but in smaller quantities [music] than after a successful pregnancy.
Despite this, human proinsulin and, surprisingly, [music] insulin were detected in the milk.
This is the first case [music] of human insulin production in genetically engineered cattle.
Mass spectrometry [music] showed the presence of C-peptide.
In the process of insulin formation, this peptide is removed [music] from proinsulin.
This suggests that cow's milk converted human [music] proinsulin into insulin.
Wheeler admitted that their goal was to produce proinsulin.
However, it turned out that the cow was able to convert it into insulin on its own.
Insulin and proinsulin, which would [music] require extraction and purification before use, were produced [music] approximately a few grams per liter of milk.
However, scientists cannot determine exactly how much insulin would be produced during a typical lactation because lactation was hormonally induced and the milk volume [music] was lower than expected.
Wheeler says that if a cow can produce 1 g of insulin per liter and a Holstein Friesian dairy cow can produce [music] 40 to 50 L of milk per day, this production method would yield large amounts of [music] insulin, especially since a typical unit of insulin is 0.0347 [music] mg.
The research team plans to recreate the genetically modified embryos and implant them into [music] cows with the hope of achieving greater success with pregnancy and full lactation [music] cycles.
Researchers are also talking about transgenic bulls that could mate with females, thus [music] creating transgenic offspring that could be used to establish a special insulin-producing herd.
Wheeler says [music] even a small herd could quickly overtake existing methods of producing insulin, transgenic yeast and bacteria. [music] Moreover, the herd could do this [music] without the need to create expensive facilities and infrastructure.
"I see a future [music] in which a herd of 100, equivalent to a small dairy.
We'll be able to produce insulin for the entire country. [music] What about a larger herd? We could supply the whole world in a year, Wheeler said.
>> [music] [music] [music] [music] >> Extremely promising results [music] of CAR T therapy in the treatment of glioblastoma multiforme.
A new immune cell-based treatment for glioblastoma [music] multiforme, the most aggressive type of brain [music] cancer, has shown extremely promising results, according to two studies. New therapies are still in their early stages of [music] development and their effects are short-lived.
But scientists believe there is reason for optimism. Glioblastoma multiforme is one of the most malignant tumors.
The median survival of patients is approximately 14 months.
Treatment involves removing the tumor, radiotherapy, and administering chemotherapy.
But even this therapy extends [music] survival by an average of 3 to 6 months.
Therefore, gliomas are one of the most difficult tumors to treat [music] and operate on.
Two new studies suggest that glioblastoma, the most aggressive [music] brain cancer, can be defeated using next-generation engineered immune cells. Anti-cancer therapies that use immune system cells [music] are classified as so-called immunotherapy.
This [music] method involves collecting lymphocytes produced in the bone marrow and maturing in the thymus from the patient.
This therapy is called CAR [music] T therapy.
The description and results of the research of two different teams were published in Nature Medicine [music] and New England Journal of Medicine.
CAR T immunotherapy is a personalized therapy and involves the genetic [music] modification of T lymphocytes, immune system cells, in a specific patient. [music] Using a viral vector, a gene encoding a receptor that recognizes an antigen specific [music] to the cancer the cell is supposed to fight is introduced into [music] these cells.
The modified cells are then reintroduced into the patient's body in the hope that they will detect [music] and destroy tumors.
But CAR T therapy has some limitations.
[music] It is expensive, technically demanding, and only applies to a few types of cancer. It is also risky. Some patients do not respond to treatment at all, and others may experience dangerous side effects.
>> [music] >> It also does not apply to solid tumors, which constitute the vast majority [music] of cancers.
At least that's how it was until now. In new research, two teams saw promising signs of tumor shrinkage after using engineered T cells that target two proteins produced by glioblastoma cells.
[music] T cells are designed to focus on only one target.
But the results presented [music] show that T cells can be engineered to treat a wider range of cancers. [music] This lends credence to the potential power [music] of T cells to impact solid tumors, especially in the brain, [music] says Brian Choi, a neurosurgeon at Massachusetts General Hospital in Boston and lead author of the study [music] published in the New England Journal of Medicine.
Gliomas pose a [music] huge challenge.
They grow quickly and can mix with healthy [music] cells in the brain, creating widespread tumors that are difficult to remove [music] surgically.
Surgery, chemotherapy, and radiation [music] therapy are usually the only treatment options for these cancers and usually result in short-term partial responses.
In CAR T therapy, a person's own T cells are removed from the body and equipped with [music] proteins that help the cells home to the tumor.
The blended cells [music] are then reintroduced into the body.
Over the past few years, >> [music] >> researchers have been developing T cells that target specific molecules produced by certain gliomas.
Both papers went a [music] step further by designing T cells that attack not one type [music] of molecule, but two.
H. Choi and his [music] colleagues engineered T cells to attach to a mutated form of a protein called epidermal growth factor receptor, [music] EGFR, which is produced by some glioblastoma cells.
The newly engineered [music] cells also secreted antibodies that bind to both T cells and the unmutated form of EGFR, which is not typically produced [music] by brain cells, but often by glioblastoma cells. [music] The result is CAR T therapy, which primes [music] the immune system to fight against cells expressing the mutated or unmutated form of EGFR.
[music] Choi and his team administered the engineered cells to three adults with relapsed glioblastoma multiforme, meaning their cancer had returned after radiation [music] and chemotherapy.
The researchers observed that the tumors [music] appeared to shrink in all three cases.
Unfortunately, after a short [music] period of reduction, the tumors returned to their former sizes.
But in one man, the tumor shrinkage lasted for more than 6 months. The second team, led by Steven Bagley, a neuro-oncologist at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, [music] developed T cells that target both EGFR and another protein found in gliomas called interleukin [music] 13 alpha 2 receptor.
These studies were conducted [music] on six people who also had recurrent glioma.
After the modified [music] T cells died, the tumors shrank in all participants. [music] After a month, one patient's tumor began to grow again. In another, the tumor showed no signs of [music] progression for 7 months.
One participant dropped out of the study, and in the remaining three people, [music] the tumors did not return to their previous size during the 6-month [music] study period.
Measuring the size of a glioma is extremely difficult [music] due to its diffuse shape.
And visible changes in tumor size may be influenced by the inflammation that occurs when [music] T cells are administered directly to the brain.
However, tumor RNA measurements in Choi's study suggest [music] that the tumors may have actually shrunk.
It turns out [music] that engineering T cells with multiple targets could ultimately [music] result in therapies with long-lasting effects by making it harder for cancer cells to develop ways to resist the therapy.
Both studies found that CAR T therapy [music] was safe and reduced tumor size in all nine patients.
In a study published in Nature Medicine, patients saw a reduction within 1 or 2 days of receiving the therapy.
In a study published in the New England Journal of Medicine, NEJM, after 1 to 5 days, one patient's tumor in the study published in NEJM had almost completely regressed after 5 days, while another patient's tumor [music] decreased in size by 60.7%.
After 69 [music] days, but the effects of these therapies were not entirely permanent. In the study, which appeared in NEJM, tumors returned [music] to size in two patients within a month and 72 days after the first injection.
>> [music] >> But one of the subjects showed no signs of cancer occurrence more than 150 days after treatment. [music] This marked the end of the therapy's testing and it is not known whether this occurred later. [music] Some of the reductions seen in the Nature Medicine study also lasted for several months.
New CAR-T cell therapies are still in the early stages of development and no data is yet available [music] on the long-term survival rates of patients in which they have been tested.
Nevertheless, scientists believe there are reasons for optimism. [music] More data is needed to assess the long-term effects of new therapies and studies will need to be conducted in larger, more diverse groups of patients.
[music] The results are exciting, but this is just the beginning. "They tell us that we are on the right track in conducting a therapy that can change the prospects of this incurable disease." emphasizes [music] Dr. Marcela Maus, co-author of the study published [music] in NEJM.
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