Intellia and Regeneration Element have published data from the latest Phase 1 clinical trial of their in vivo genome editing therapy NTLA-2001

On February 28, Intellia and Regeneration Element released data
from the latest Phase 1 clinical trial of their in vivo genome editing therapy, NTLA-2001.
The results showed that all doses were well tolerated, and that in the two highest dose groups, serum levels of the target protein were reduced
by an average of 86% and 93%, respectively.

The press release also noted that the reduced serum TTR protein levels remained stable
at intervals of 2 to 12 months of follow-up.

Source: Intellia

It is reported that NTLA-2001 is the first CRISPR/Cas9 candidate gene therapy for precision editing of human genes
.
Through lipid nanoparticles (LNPs), the CRISPR gene editing system targeting the TTR gene is delivered to the human body, which can specifically knock out the TTR gene in the liver, thereby reducing the expression of TTR protein and reducing the accumulation
of pathogenic proteins.

Transthyroxine amyloidosis (ATTR) is a rare, systemic, progressive, and lethal disease
.
Because of a specific mutation in the TTR gene, patients with the disease produce misfolded transthyroxine proteins
in the liver.
As these proteins accumulate in the human body, they can lead to organ failure and eventually death
.

In June last year, the first clinical results of NTLA-2001 were announced, which attracted the attention
of the global industry.
This NTLA-2001 data update once again demonstrates the potential
of CRISPR in vivo edited liver delivery.

What is gene therapy?

Gene therapy products are composed of two major parts of the vector and gene, the active ingredient can be DNA, RNA, genetically modified viruses, bacteria or cells, by introducing foreign genes into target cells or tissues, replacing, compensating, blocking, and modifying specific genes to achieve the purpose of
treating diseases.

The idea of gene therapy has been around since 1972, and after half a century, gene therapy has gone from concept to reality
.

In 2017, the U.
S.
FDA approved the first in vivo gene therapy, Luxturna, to restore and improve their vision in children and adults who have lost vision due to pure and mutated RPE65 genes but retain a sufficient number of surviving retinal cells
.
The product was developed by SparkTherapeutics (which has been acquired by Novartis), the first true gene therapy in the U.
S.
market and the official arrival
of the era of gene therapy.

In 2019, the U.
S.
FDA approved Novartis' Zolgensma for the treatment of children under 2 years of age with spinal muscular dystrophy (SMA) caused by the allele mutation of surviving motor neuron 1 (SMN1
).
The therapy restores the patient's ability
to exercise by delivering the correct human SMN1 gene to the patient's neurons via adeno-associated virus (AAV).
At a price of up to $2.
1 million, the therapy is currently the most expensive drug
in the world.

In 2019, the European Union approved Bluebird's Zynteglo for the treatment of non-β0β0 genotype-dependent β-thalassemia patients
aged 12 years and older.
It is the world's first gene therapy
approved to treat thalassemia.

In 2021, the European Union approved Bluebird's one-time gene therapy Skysona for the treatment of patients under the age of 18, who carry ABCD1 gene mutations, who do not have an HLA-matched sibling hematopoietic stem cell (HSC) donor, and who
have early cerebral adrenoleukodystrophy (CALD).
This is the first and only gene therapy approved by the European Union to treat CALD
.

Gene therapy becomes the "fragrant food" of MNC

Nowadays, gene therapy has become the key layout direction
of major pharmaceutical companies.
According to the well-known consulting firm Froster Sullivan, the global gene therapy market size will reach $30.
54 billion by 2025, of which the Chinese market will reach $17.
89 billion
.

During the 40th J.
P.
Morgan Healthcare Annual Conference (JPM), several gene therapy-related collaborations were reached
.

Pfizer and Beam have reached a $1.
35 billion cooperation agreement to jointly develop up to three in vivo base editing therapies
.
Together, the two companies will advance therapies
for rare genetic disorders that target the liver, muscles, and central nervous system.

Bayer has partnered with MammothBiosciences to develop the next generation of in vivo gene editing therapies
.

Last year, Roche partnered with ShapeTherapeutics (ShapeTX) to develop gene therapies
for certain targets in the fields of Alzheimer's disease, Parkinson's disease and rare diseases.

In China, a large number of outstanding local gene therapy enterprises and scientific research institutions have also emerged in the field of gene therapy, and many indications have been deployed, including hemophilia A/B, β-thalassemia, autoimmune deficiency diseases and various solid tumors
.

It is undeniable that in the field of rare diseases, gene therapy is beginning to benefit
more and more patients who would otherwise have no cure.

And in addition to rare diseases, in fact, compared with traditional drugs that directly supplement important substances (proteins, inorganic substances, polypeptides, etc.
) needed by the human body or regulate protein targets in the signaling pathway, the site of action of gene therapy is more "upstream", and treatment
is carried out at the nucleic acid level.
According to the central law, diseases caused by protein abnormalities in theory can be treated
by the action of nucleic acids.
Based on this, the field of gene therapy can be treated is very extensive, and in addition to rare genetic diseases, more common disease types will also have a place
for gene therapy.

epilogue

In recent years, with the breakthrough of CRISPR technology, the development of genome editing has entered the fast lane
.
But gene therapy still has a lot of problems to solve
.

On the one hand, gene therapy still needs to make breakthroughs in technology, and the ethical controversy when used in germ cells is extremely
controversial.

On the other hand, the gene therapy production process has a high degree of diversity and complexity, the construction of the production platform requires a lot of capital and time investment, and the selection and quality inspection of the follow-up process are not friendly
to small-scale enterprises.
Innovators may need to work
more with CDMO.