"Black Technology" Comes Out!

Editor's note: Every disruptive technological innovation in human history will bring about the great liberation of productive forces and fundamentally change the trajectory of social developme.

Breakthrough innovation - the advent of next-generation technology TESSA™

Breakthrough innovation - the advent of next-generation technology TESSA™

Since the advent of gene therapy, human beings have an unprecedented "weapon" against diseas.

.

How to change the traditional manufacturing process and break through the current bottleneck of large-scale production has become an urgent challenge for the industry to sol.

▲Gene therapy (Image source: FDA official website)

▲Gene therapy (Image source: FDA official website)

As a technology to treat or cure disease by altering a person's genes, gene therapy can work through several mechanisms:

Replacing a disease-causing gene with a healthy copy of the gene

Inactivate disease-causing genes that are not working properly

Introducing a new or modified gene into the body to help treat a disease

In the process of gene therapy, gene "transportation" will inevitably occur, and the tools used are called "carrier.

▲ TESSA™ related research published in Nature Communications

▲ TESSA™ related research published in Nature Communications

How will the advent of TESSA™ technology change the development and production of gene therapy?

Looking at the present - why is the dilemma of large-scale mass production of rAAV vectors?

Looking at the present - why is the dilemma of large-scale mass production of rAAV vectors?

rAAV is derived from the artificial modification of wild-type adeno-associated virus (AA.

"In nature, AAV is produced in a very efficient way, and almost every AAV particle contains a genome," said .

But the problem follow.

When adenovirus assists AAV amplification, it will also self-replica.

Therefore, the current mainstream technology is to use plasmid transfection to produce rA.

Although plasmid transfection avoids the introduction of adenovirus and related unsafe factors from the process, the limitation is that it is difficult to scale .

Although plasmid transfection avoids the introduction of adenovirus and related unsafe factors from the process, the limitation is that it is difficult to scale .

Because gene therapy products must reach a certain dose to achieve the desired therapeutic effect, the traditional plasmid process often only meets the treatment of one patient at a time, which has a high cost; while the TESSA™ technology can achieve one-time production through one-time producti.

The traditional plasmid process often can only meet the treatment of one patient at a time, which has a high cost; while the TESSA™ technology can meet the treatment needs of more patients through one-time production,

Precise regulation - making adenovirus the "strongest assistant"

Precise regulation - making adenovirus the "strongest assistant"

When thorny issues arise on the road to innovation, challenges need to be faced head-.

TESSA™ technology first uses adenovirus as a "helper" role as a breakthrou.

Therefore, TESSA™ technology makes full use of the life cycle of adenovirus, which is strictly regulated , activating its gene expression in the early stage, and shutting down the gene expression in the late sta.

TESSA™ technology makes full use of the life cycle of adenovirus, and the modified adenovirus has become an excellent "rAAV production assistant.

It fully reduces the contamination of rAAV products by adenovirus while efficiently mass-producing rA.

Inhibits 9999-100% of adenovirus production during rAAV production

TESSA™, the full name of Tet Enabled Self Silencing Adenovirus (tetracycline self-silencing adenovirus technolog.

The researchers inserted a tetracycline repressor (TetR) binding site into the major late promoter (MLP) of the recombinant adenovirus, making it only able to complete early expression in the absence of tetracycli.

The researchers further stably integrated the Rep and Cap genes of AAV into TESS.

The Cap gene encodes the capsid protein of rAAV, and the Rep gene is involved in replication and integration, both of which play a decisive role in the replication and packaging of rA.

The integrated TESS A™ can efficiently deliver all the necessary components for rAAV replication at the same time, becoming a "one-stop production line" that can efficiently enter the "cell factory", significantly improving rAAV productivity, solid rate and transfection capaci.

The integrated TESS A™ can efficiently deliver all the necessary components for rAAV replication at the same time, becoming a "one-stop production line" that can efficiently enter the "cell factory", significantly improving rAAV productivity, solid rate and transfection capaci.

▲ Schematic diagram of the production of rAAV by TESSA pro and TESSA 0

▲ Schematic diagram of the production of rAAV by TESSA pro and TESSA 0

There are many serotypes of rAAV, and we take the rAAV2 subtype as an example (see the figure belo.

Compared with plasmid-dependent unassisted systems, the production of rAAV2 using TESSA™ technology can increase vector yield by approximately 40 times ; in terms of quality, AAV vectors increase the cumulative transfection capacity of cells with the gene of interest by more than 2400 times (based on TESS.

™ technology, the transfection rate of rAAV2 containing genome can be 1/6, while the rate of rAAV2 based on plasmid transfection technology is 1/1200); in addition, the packaging efficiency of rAAV vector has also been significantly improved, the real rate of the vector (the capsid contains the genome) from 2-5% to 70%

The vector yield is increased by about 40 times , and the transfection capacity is cumulatively increased by more than 2400 time.

The solid rate of the vector (containing the genome in the capsid) is increased from 2-5% to 70%

TESSA™ technology is not only a breakthrough in yield and quality, but also a breakthrough in sca.

Unlike the plasmid-dependent process route, with TESSA™ technology, the production scale of rAAV can jump to 2000L

What does this mean for gene therapy?

Through TESSA™ technology, the production scale of rAAV can jump to 2000L

▲Schematic diagram of the difference in the scale of rAAV production by different technologies

▲Schematic diagram of the difference in the scale of rAAV production by different technologies

Although, many gene therapy products are still individualized and customiz.

We can imagine a day when gene therapy products, like many conventional injectable drugs today, can be mass-produced in advan.

Patients in need can easily and conveniently obtain it immediately in medical institutio.

TESSA™ technology brings us one step closer to this dre.

It changes the paradigm of rAAV production, realizing the transition from inefficiency to high efficiency, providing the industry with a new option that is scalable, pollution-free, transfection-free, and transfection-independe.

Leading in Innovation - Improving Patient Access to Gene Therapy

Leading in Innovation - Improving Patient Access to Gene Therapy

There is no doubt that TESSA™ technology is an exciting breakthrough for innovators focused on cell and gene therapy development around the wor.

When we re-examine the prospects of TESSA™ from a therapeutic perspective, we have reason to believe that its safety and high efficacy will directly improve development efficiency, reduce costs, and further promote the accessibility of cell and gene therapy, benefiting the world patie.

Disruptive innovation is always the road that few people take, but it has become the consensus and responsibility of the whole industry to cooperate and promote innovati.

Recently, WuXi Pharma and the Agency for Science, Technology and Research (A*STAR) of Singapore announced a new cooperation, which will bring WuXi Pharma’s advanced TESSA™ patented technology to the Asia-Pacific regi.

The cooperation aims to promote scientific research innovation in the field of cell and gene therapy, establish a joint talent development program, and train the next generation of scientists and engineers in the field of GMP production for the indust.

As a globally operating cell and gene therapy CTDMO, WuXiXi's unique business model combines strong testing capabilities with process development and production platform capabilities, such as TESSA™ technology for rAAV production and stable lentivirus producti.

Lenti solutions,e.

Through WuXi Gene's integrated empowerment platform, all testing and development, biosafety, virus clearance, and final product release testing can be realized on this platform, helping customers significantly shorten the time-to-market for advanced therapi.

As .

Zhang Youxiang, CEO of WuXi Biotech, envisions: "Technological breakthroughs will drive the vigorous development of industrial innovati.

We expect that with the realization of high-quality and large-scale production of vectors, the patient accessibility of the new generation of gene therapy will be improv.

At the same time, it can also further optimize the production process and therapeutic effect of existing therapies, and hopefully in the near future, it can benefit more patien.

"

One end of innovation is a vision that breaks the rules, and the other end is a change rooted in reali.

A better "tomorrow" needs to start with a better "toda.

References:

References:

[1]What is gene thera.

https:// is gene thera.

https:// [2] Su,.

, Patrício, MI, Duffy, MR et .

Self-attenuating adenovirus enables production of recombinant adeno-associated virus for high manufacturing yield without contaminati.

Nat Commun 13, 1182 (202
https:// d.

org/11038/s41467-022-28738-2

[2] Su,.

, Patrício, MI, Duffy, MR et .

Self-attenuating adenovirus enables production of recombinant adeno-associated virus for high manufacturing yield without contaminati.

Nat Commun 13, 1182 (202
https:// d.

org/11038/s41467-022-28738-2