Es mostren les entrades ordenades per rellevància per a la consulta crispr. Ordena per data Mostra totes les entrades
Es mostren les entrades ordenades per rellevància per a la consulta crispr. Ordena per data Mostra totes les entrades

17 de març 2021

The long and bumpy road to CRISPR (3)

 CRISPR People. The Science and Ethics of Editing Humans

A book on the ethics of CRISPR, without a clear prescription, only a review of He horrendous experiment and a personal view of the current situation.

This has been a cautionary tale about scienceand scientists. People can overreach. He Jiankui, driven as far as I can tell by what Macbeth called “vaulting ambition, which o’erleaps itself,”1 and aided by a serious lack of scruples, behaved terribly. He put three lives at needless and reckless risk (and tried to do the same to more). The story is also a cautionary tale for Science. He Jiankui damaged Science by reinforcing the Victor Frankenstein image—the mad, uncontrolled scientist. Most scientists, and hence most science, are much more rule bound, constrained by the needs of getting and keeping jobs, tenure, and most importantly grants, as well as wrapped, in most countries, in many bureaucratic threads of control. But He happened, and Science needs both to act to minimize the harm he has caused and to be seen to be doing so.

A global consensus is a chimera. Seven and a half billion people are not going to agree on this issue—nor will the fraction of those who understand it. Neither will the roughly 200 countries of the world, at least at anything other than a lowest common denominator. Not all countries have agreed to various nuclear weapons or climate change treaties in spite of the apparently obvious need for them. If somehow something close to unanimity were achieved, it would probably be at the cost of precision. Thus, the Council of Europe enacted a convention that banned human cloning, but effectively left open the then-hot question whether it covered just reproductive cloning or “research cloning” (of human embryos for only ex vivo use) by not defining a “human being.” It also left the implantation and enforcement of such a ban up to the member nations, some of whom were probably happy, for political reasons, to sign it but will have little interest in enforcing it. 

And this is the controversial position of the author:

 One might argue that human germline genome changes are irreversible, or less reversible, than some other interventions. But is that true? A mistaken genome change could presumably be reedited, in a living person or in that person’s germline (or embryos), to reverse the error. Or it could be selected against in the individual’s offspring, through PGD or otherwise. It could be too late to avoid harm to the edited person, but that mistake will not have to pass on from generation to generation. Human germline genome editing does raise important questions about safety, coercion, equity, diversity, and  enhancement. These are not unique to editing the human germline genome. They also apply to somatic cell DNA editing, to new drugs, to smartphones, to climate change, and to many other changes from technologies. Questions about reversibility also apply; the social effects of cell phones are probably less reversible than genome edits. The fact that a technological change is in “the human germline genome” should have no special ethical weight.

Really? Security in CRISPR is not unique???






23 de febrer 2017

Genome editing, closer than you think

Human Genome Editing Science, Ethics, and Governance

Last week the US patent office ruled that hotly disputed patents on the CRISPR revolutionary genome-editing technology belong to the Broad Institute of Harvard and MIT. In a former post I explained the dispute. Genome editing in my opinion shouldn't be patented and will see exactly the impact of such ruling in US and elsewhere in the next future.
If you want to know in detail what does genome editing means for the future of life sciences, have a look at NASEM book.
It is now possible to insert or delete single nucleotides,interrupt a gene or genetic element, make a single-stranded break in DNA, modify a nucleotide, or make epigenetic changes to gene expression. In the realm of biomedicine, genome editing could be used for three broad purposes: for basic research, for somatic interventions, and for germline interventions.
CRISPR (which stands for clustered regularly interspaced short palindromic repeats) refers to short, repeated segments of DNA originally discovered in bacteria. These segments provided the foundation for the development of a system that combines short RNA sequences paired with Cas9 (CRISPR associated protein 9, an RNA-directed nuclease), or with similar nucleases, and can readily be programmed to edit specific segments of DNA. The CRISPR/Cas9 genome-editing system offers several advantages over previous strategies for making changes to the genome and has been at the center of much discussion concerning how genome editing could be applied to promote human health.
I would just want to say that these patents destroy the soul of science, since access should be available with no barriers for the development of  innovation. Patents are not the incentive for discovery in this case, as I explained in my post, natural processes should'nt be patented. And this is why today is a really sad day.

PS. My posts against patents






Michael Kiwanuka. Home again

08 de gener 2024

Els medicaments que venen i els que ja s'han aprovat el 2023

És bo fer una ullada a quins són els medicaments que previsiblement s'aprovaran l'any 2024, i els de Nature diuen que són aquests:

Medicaments per aprovar el 2024

Biologic name

Sponsor

Properties

Indication

Timing

Zolbetuximab

Astellas

Claudin 18.2-targeted mAb

Gastric cancer

January

Lifileucel

Iovance

Tumour-infiltrating lymphocyte therapy

Melanoma

February

Resmetiroma

Madrigal/Synta

Thyroid hormone receptor β agonist

NASH

March

Sotatercepta

Merck & Co./Acceleron

Fusion protein ligand trap for TGF-β superfamily

PAH

March

mRNA-1345a

Moderna

mRNA-based vaccine

RSV prevention

April

Donanemaba

Eli Lilly

Amyloid-β-targeted mAb

Alzheimer disease

Q1

EB-101a

Abeona

Gene therapy with COL7A2 transgene

RDEB

May

Patritumab deruxtecana

Merck & Co.

HER3-targeted ADC

NSCLC

June

Imetelstat

Geron

Telomerase inhibitor

Transfusion-dependent anaemia with MDS

June

Tarlatamaba

Amgen

DLL3 × CD3 T-cell engager antibody

SCLC

June

Fidanacogene elaparvoveca

Pfizer/Spark

AAV-based gene therapy with factor IX transgene

Hemophilia B

Q2

Bentracimaba

Laboratoires SERB

Ticagrelor-neutralizing antibody

Drug toxicity

1H

Crovalimaba

Roche

C5-targeted mAb

PNH

July

Danicopana

AstraZeneca/Alexion

Factor D inhibitor

PNH

July

Midomafetaminea

MAPS

MDMA

PTSD

August

Xanomeline plus trospium

Karuna/BMS

Muscarinic receptor modulators

Schizophrenia

September

Acoramidis

BridgeBio

TTR stabilizer

TTR amyloidosis

December

Marstacimab

Pfizer

TFPI-targeted mAb

Haemophilia A and B

Q4

Afamitresgene autoleucela

Adaptimmune

MAGE-A4-targeted autologous, engineered T cell therapy

Synovial sarcoma

2024


Fig. 1 | 30 years of novel FDA approvals. Annual numbers of new molecular entities (NMEs) and biologics license applications (BLAs) approved by the FDA’s Center for Drug Evaluation and Research (CDER). See Table 1 for new approvals in 2023. Products approved by the Center for Biologics Evaluation and Research (CBER), including vaccines and gene therapies, are not included in this drug count (Table 2). Source: FDA.

Fig. 2 | CDER approvals by therapeutic area. Indications that span multiple therapeutic areas are classified under only one, based on which FDA office and division reviewed the approval application. Sources: Nature Reviews Drug Discovery, FDA.


Fig. 3 | CDER approvals by modality. Small molecules, including peptides of up to 40 amino acids in length, and oligonucleotides are approved as new molecular entities (NMEs). Protein-based candidates are approved through biologics license applications (BLAs). mAb, monoclonal antibody; siRNA, small interfering RNA. Source: Nature Reviews Drug Discovery.

I la notícia de l'any ha estat CRISPR:
Vertex and CRISPR Therapeutics’ exagamglogene autotemcel (exa-cel; Casgevy) especially is the first CRISPR–Cas9-based gene editor to secure a green light from the FDA, winning an approval for sickle cell disease (SCD). Exa-cel is an ex vivo gene-edited cell therapy: blood cells are harvested from patients, genetically modified at the BCL11a transcription factor to re-enable fetal haemoglobin production, and then re-infused into patients. The therapeutically upregulated fetal haemoglobin compensates for the defects in β-haemoglobin that cause the diseases. Clinical data shows that the gene therapy has curative potential, although longer-term data are needed to assess the durability of the effect.

When Harvard Medical School and HHMI’s Stuart Orkin and colleagues discovered the role of BCL11a in fetal haemoglobin production in 2008, it was unclear how to drug the transcription factor. The arrival of CRISPR–Cas9 gene-editing system in 2012 provided a path forward for haemoglobinopathies. The development of the programme was “remarkably fast”, said Orkin. “It is a perfect example of how the ecosystem can work.”

Vertex and CRISPR have priced the one-off treatment at $2.2 million. It also requires a harsh preconditioning chemotherapy regimen, to make room for the edited cells. The therapy will consequently remain out of reach for many patients. “This is not the end game,” says Orkin, who has his eye on next-generation gene editors and small molecules that might be more accessible.
PS. Un breu missatge per aquells que mitjançant la seva recerca "obren la porta" a tractaments i ho expliquen al Telenotícies. No n'hi ha cap d'aquesta llista del 2024 ni del 2023 d'aquí sota que sigui un d'ells, la porta segueix oberta, o potser no hi havia porta per obrir. Millor no haver d'estar sentint això sempre, sense explicar-ne el resultat.
PS. The economist sobre el tema




PS. El llistat de medicaments:

Table 1 | CDER approvals in 2023

Drug (brand name)

Sponsor

Properties

Indication

Lecanemab (Leqembi)a

Eisai/Biogen

Amyloid-β-targeted mAb

Alzheimer disease

Bexagliflozin (Brenzavvy)

Theracosbio

SGLT2 inhibitor

Glycaemic control in type 2 diabetes mellitus

Pirtobrutinib (Jaypirca)

Loxo/Eli Lilly

BTK inhibitor

Mantle cell lymphoma

Elacestrant (Orserdu)

Stemline

ER antagonist

ER-positive, HER2-negative, ESR1-mutant breast cancer

Daprodustat (Jesduvroq)

GSK

HIF-PH inhibitor

Anaemia caused by CKD for adults on dialysis

Velmanase alfa (Lamzede)a

Chiesi

Recombinant α-mannosidase

Non-CNS manifestations of α-mannosidosis

Sparsentan (Filspari)

Travere

Endothelin and angiotensin II receptor antagonist

Proteinuria in primary IgA nephropathy

Omaveloxolone (Skyclarys)

Reata/Biogen

Mechanism unknown, NRF2 activator

Friedrich’s ataxia

Zavegepant (Zavzpret)

Pfizer

CGRP receptor antagonist

Migraine

Trofinetide (Daybue)

Acadia

Mechanism unknown

Rett syndrome

Retifanlimab (Zynyz)a

Incyte

PD1-targeted mAb

Merkel cell carcinoma

Rezafungin (Rezzayo)

Cidara

Echinocandin antifungal

Candidemia and invasive candidiasis

Leniolisib (Joenja)

Pharming

PI3Kδ inhibitor

Activated PI3Kδ syndrome

Tofersen (Qalsody)

Biogen

SOD1-targeted ASO

SOD1 amyotrophic lateral sclerosis

Pegunigalsidase alfa (Elfabrio)a

Chiesi

PEGylated recombinant α-galactosidase Α

Fabry disease

Fezolinetant (Veozah)

Astellas

Neurokinin 3 receptor antagonist

Hot flashes caused by menopause

Perfluorohexyloctane (Miebo)

Bausch + Lomb

Semifluorinated alkane

Dry eye disease

Epcoritamab (Epkinly)a

Genmab/AbbVie

CD20 × CD3 T-cell engager

DLBCL and high-grade B-cell lymphoma

Sulbactam, durlobactam (Xacduro)

Entasis

β-lactam antibacterial plus a β-lactamase inhibitor

Hospital-acquired and ventilator-associated bacterial pneumonia caused by susceptible ABC

Nirmatrelvir, ritonavir (Paxlovid)

Pfizer

SARS-CoV-2 main protease inhibitor plus a CYP3A inhibitor

Mild-to-moderate COVID-19

Flotufolastat F18 (Posluma)

Blue Earth

Radioactive diagnostic agent

PET imaging in prostate cancer

Sotagliflozin (Inpefa)

Lexicon

SGLT1/2 inhibitor

Heart failure

Glofitamab (Columvi)a

Genentech

CD20 × CD3 T-cell engager

DLBLC or large B-cell lymphoma

Ritlecitinib (Litfulo)

Pfizer

JAK3 inhibitor

Alopecia areata

Rozanolixizumab (Rystiggo)a

UCB

FcRn-targeted mAb

AChR- or MuSK-antibody-positive gMG

Somatrogon (Ngenla)a

Pfizer

Human growth hormone analogue

Growth hormone deficiency

Nirsevimab (Beyfortus)a

AstraZeneca

RSV F protein-targeted mAb

RSV lower respiratory tract disease

Quizartinib (Vanflyta)

Daiichi Sankyo

FLT3 kinase inhibitor

AML

Lotilaner (Xdemvy)

Tarsus

Ectoparasiticide

Demodex blepharitis

Zuranolone (Zurzuvae)

Sage

GABAA receptor PAM

Postpartum depression

Avacincaptad pegol (Izervay)

Iveric/Astellas

C5-targeted aptamer

Geographic atrophy secondary to AMD

Talquetamab (Talvey)a

Janssen

GPRC5D × CD3 T-cell engager

Multiple myeloma

Elranatamab (Elrexfio)a

Pfizer

BCMA × CD3 T-cell engager

Multiple myeloma

Palovarotene (Sohonos)

Ipsen

Retinoic acid receptor agonist

Fibrodysplasia ossificans progressiva

Pozelimab (Veopoz)a

Regeneron

C5-targeted mAb

CHAPLE disease

Motixafortide (Aphexda)

Biolinerx

CXCR4 inhibitor

Hematopoietic stem cell mobilization for autologous transplantation in multiple myeloma

Momelotinib (Ojjaara)

GSK

JAK1/2, ALK2 inhibitor

Myelofibrosis in adults with anaemia

Gepirone (Exxua)

Fabre-Kramer

5HT1A receptor agonist

Major depressive disorder

Cipaglucosidase alfa (Pombiliti)a

Amicus

Recombinant α-glucosidase

Pompe disease

Nedosiran (Rivfloza)

Novo Nordisk

LDHA-targeted siRNA

Primary hyperoxaluria type 1

Etrasimod (Velsipity)

Pfizer

S1P receptor modulator

Ulcerative colitis

Zilucoplan (Zilbrysq)

UCB

Complement C5 inhibitor

AChR-antibody positive gMG

Bimekizumab (Bimzelx)a

UCB

IL-17A/F-targeted mAb

Plaque psoriasis

Vamorolone (Agamree)

Santhera

Corticosteroid

Duchenne muscular dystrophy

Mirikizumab (Omvoh)a

Eli Lilly

IL-23-targeted mAb

Ulcerative colitis

Toripalimab (Loqtorzi)a

Coherus

PD1-targeted mAb

Nasopharyngeal carcinoma

Fruquintinib (Fruzaqla)

Takeda

VEGFR1/2/3 kinase inhibitor

Colorectal cancer

Taurolidine, heparin (Defencath)

Cormedix

Thiadiazinane antimicrobial plus an anticoagulant

Incidence of catheter-related bloodstream infections

Repotrectinib (Augtyro)

Bristol Myers Squibb

ROS1 and TRK kinase inhibitor

ROS1-positive NSCLC

Efbemalenograstim alfa (Ryzneuta)a

Evive

Recombinant leukocyte growth factor

Neutropenia

Capivasertib (Truqap)

AstraZeneca

AKT kinase inhibitor

Breast cancer

Nirogacestat (Ogsiveo)

Springworks

γ-secretase inhibitor

Desmoid tumours

Iptacopan (Fabhalta)

Novartis

Complement factor B inhibitor

Paroxysmal nocturnal haemoglobinuria

Birch triterpenes (Filsuvez)

Chiesi

Mechanism unknown

Epidermolysis bullosa

Eplontersen (Wainua)

Ionis/AstraZeneca

TTR-targeted ASO

hATTR with polyneuropathy