Pipelines - Genecradle Therapeutics CO.,LTD.

About Gene Therapy

What is Gene Therapy

Human diseases are mainly caused by imbalances in the metabolism of important substances in life activities or imbalances in the regulation of corresponding signal pathways. A considerable part of these diseases are caused by defects in gene expression. Traditional drugs act on the protein level, and patients often need long-term medication. Gene therapy starts with DNA, the source of protein synthesis, and changes the transmission of genetic information by regulating DNA, thereby changing the properties of proteins and curing the disease from the root.
How is gene therapy achieved?

Gene therapy is the process of delivering expression units including "therapeutic genes" into the patient's body through drug carriers, so that they can exist and express therapeutic proteins for a long time. It is similar to the process of a gene transplant, so it has a long-term therapeutic effect that traditional chemical drugs or protein structure drugs cannot achieve.
The most widely used gene therapy drug carrier is the adeno-associated virus vector (AAV vector), which is widely used due to its good safety, low immunogenicity, and good tissue specificity.
Characteristics and advantages of gene therapy

(1) Fundamental precision treatment: "Gene disease, gene therapy" drugs act on the source of the disease - abnormal genes. According to the characteristics of the disease, through the selection and innovative design of delivery vectors and regulatory elements, the therapeutic genes are specifically delivered into the body to achieve precise targeted treatment of genetic diseases.
(2) High efficiency and long-term effect: It has a high gene transduction efficiency, can effectively deliver therapeutic genes to target cells, and stably express them in the cell nucleus as free bodies, thereby achieving long-term efficacy.
(3) Safety and durability: The delivery vector is non-pathogenic and has low immunogenicity, which reduces side effects and risks during treatment and provides reliable guarantees for clinical applications. Gene therapy can achieve long-term expression of therapeutic genes, so a single dose can produce lasting therapeutic effects, which can effectively reduce the pain of patients' frequent or lifelong medication and improve their quality of life.
Application areas of gene therapy

Gene therapy has a wide range of applications and can treat a variety of diseases, including genetic diseases, tumors, cardiovascular diseases, nervous system diseases, immune system diseases, etc. The current hot application areas include ophthalmic diseases, nervous system diseases with genetic etiology, muscle diseases, and metabolic monogenic genetic diseases (rare diseases). As an emerging treatment method that uses modern molecular biology technology and precision medicine theory and practice, gene therapy will continue to develop in breadth and depth, and related research and applications still need to be continuously explored and improved.
Why is gene therapy effective in the long term?

One of the important advantages of AAV as a gene therapy vector is that it mediates long-term expression of the target gene. The academic community believes that after the AAV virus infects and enters the cell nucleus, the capsid disintegrates and releases its genome, synthesizing the second chain with the help of the single-stranded AAV genome of the host cell function, and undergoing intermolecular or intramolecular recombination under the drive of ITR to form a circular episome, which persists in the host cell nucleus in a form independent of the host cell chromosome. Therefore, at the cellular level, AAV-mediated expression of the target gene runs through the entire cell life cycle, which is the theoretical basis for the long-term effectiveness of AAV gene therapy.
In biological individuals, since the lifespan of non-dividing cells (such as neurons) is basically the same as the lifespan of individuals, gene therapy targeting non-dividing cells is long-lasting, even lifelong. For example, a study found that after a single injection of AAV gene drugs into the brain parenchyma of non-human primates, the target gene continued to be expressed for more than 15 years.
Compared with traditional therapies, the therapeutic effect of AAV gene therapy targeting dividing cells is also long-term.

Technology Platform

While continuing to strengthen our technology research and development capabilities, we place greater emphasis on maintaining the efficiency, simplicity and practical value of the GeneCradle technology platform, and are committed to leveraging the powerful capabilities of the technology platform to transform cutting-edge genetic technologies into gene therapy drugs that can solve actual clinical problems.

Gene target research

Gene target research is a process that starts from scratch and often requires decades or even longer proof of principle and clinical sample research.
GeneCradle studies the pathogenic targets of various genetic diseases and degenerative diseases in the early stage of literature research and development projects to better understand the causes of diseases and simulate the disease process, so as to design gene drugs to intervene, delay or even cure one or a class of diseases.
Drug design verification

Gene medicine is a rational design process based on disease characteristics and treatment principles. It is a dialectical unity of gene complexity and the diversity of drug action principles. GeneCradle has carried out design innovations at multiple levels, including gene elements, therapeutic genes, and delivery shells, and has built a thousand-square-meter self-owned laboratory animal and model animal pharmacology verification center in Beijing, so that more varieties of gene medicines can obtain research data more quickly.
Medical Clinical Trials

Clinical trials are an important and necessary way to promote medical progress and are of great significance and value.
GeneCradle has in-depth cooperation with the country's top clinical research institutions and excellent and experienced medical teams to complete the development of clinical indicator methodology on the basis of protecting the interests of the patient group, in order to obtain confirmatory data on the safety and effectiveness of gene drugs and support the listing and commercialization of gene drugs.
Manufacturing and distribution

Manufacturing capabilities are the cornerstone of our ability to bring gene drugs to patients more quickly and economically.
GeneCradle uses a highly efficient AAV gene drug vector production system and builds a 10,000-square-meter gene drug production base in Beijing. Advanced manufacturing links, GMP standards and ISO9001 quality assurance system make the manufacturing of gene drugs more reliable.

Product Pipelines

The GeneCradle technology platform is currently developing and validating more than 30 gene drugs, which is expected to provide more effective and safe gene therapy drugs for more than 5 million people.

10+

Clinical trials or clinical studies are ongoing
60+

Independent intellectual property rights
5 Item

Products entering the key verification stage

POC
pre-IND
IND
BLA

GC101 Spinal Muscular Atrophy (SMA)

Mechanism of action

AAV gene drug carrying SMN1 gene expression cassette

Indications

SMA Type Ⅰ, Type Ⅱ, and Type Ⅲ

Project Overview

Spinal muscular atrophy (SMA) is a common autosomal recessive genetic disease in children and adolescents, with an incidence of 1/6000 to 1/10000, and a carrier frequency of about 1/40 to 1/50 in the population. The disease is characterized by muscle atrophy and paralysis caused by degeneration of the anterior horn motor neurons of the spinal cord. The International SMA Federation has formulated the classification principles of SMA based on the patient's age of onset, motor ability and life expectancy, and divides SMA into Type Ⅰ, Type Ⅱ, Type Ⅲ, etc. GC101 is an SMA gene therapy drug developed by our company. It is an AAV gene drug carrying the SMN1 gene expression cassette. Through the selection of the recombinant AAV virus vector serotype, the mutation and modification of the reverse terminal repeat sequence of the main cis-acting element, and the selection of a suitable AAV virus vector, the artificially designed SMN1 gene expression cassette is efficiently transported to the target organs and tissues. After being injected intravenously, intrathecally or intraventricularly, the recombinant AAV virus can efficiently transduce the central nervous system, express SMN protein in neurons, and restore the physiological function of neurons.
GC301 Glycogen Storage Disease Type Ⅱ (Pompe Disease)

Mechanism of action

AAV gene drug carrying GAA gene expression cassette

Indications

Infantile-onset Pompe disease (IOPD)， Late-onset Pompe disease (LOPD)

Project Overview

Glycogen storage disease type Ⅱ, also known as Pompe disease, is a systemic lysosomal storage disorder primarily affecting muscles and also the central nervous system. Patients lack functional acid alpha-glucosidase (GAA) in lysosomes, leading to the accumulation of glycogen in cells, particularly in skeletal muscle, cardiac muscle, and the central nervous system (including the brain and spinal cord). GC301, developed by Genecradle Therapeutics, is a Pompe disease therapy that carries a GAA gene expression cassette via an AAV vector. Through a single intravenous injection, it systemically compensates for the GAA enzyme deficiency, targeting key affected tissues such as the liver, heart, skeletal muscle, and central nervous system. A single dose of GC301 enables long-term expression of the GAA enzyme, significantly improving patients’ motor function and quality of life, offering an innovative root-cause therapeutic option for the Pompe disease population.
GC304 Hypertriglyceridemia (HTG)

Mechanism of action

AAV gene drug carrying LPL-S447X gene expression cassette

Indications

Hypertriglyceridemia

Project Overview

Lipoprotein lipase (LPL) is a key enzyme for hydrolyzing plasma triglyceride (TG). Dysfunction of this enzyme can increase the content of triglyceride-rich lipoprotei (TRL) such as plasma chylomicrons and very low-density lipoproteins, and clinical manifestations include chylomicron/low-density lipoproteinemia and elevated plasma triglycerides. GC304 is a gene therapy drug for hypertriglyceridemia developed by our company. It is an AAV gene drug carrying the LPL-S447X gene expression frame. Through the optimization of the viral vector structure, the efficient and specific expression of the functional LPL gene in the target is achieved from multiple different levels, while reducing the possible immune response and improving the effectiveness and safety of the viral vector as a gene drug. Animal experiments have shown that this gene drug is not only effective for hypertriglyceridemia caused by LPL gene defects, but also has significant therapeutic effects on hypertriglyceridemia caused by high-fat diet, hypertriglyceridemia caused by GPIHBP1 gene defects, and diseases caused by them, such as acute pancreatitis.
GC310 Hepatolenticular degeneration (Wilson's Disease)

Mechanism of action

AAV gene drug carrying ATP7B truncated gene expression cassette

Indications

Wilson's disease

Project Overview

Hepatolenticular degeneration, also known as Wilson's disease, is a disorder of copper metabolism caused by mutations in the copper-transporting ATPase β (ATP7B) gene. It primarily affects the liver, brain, kidneys, and cornea, leading to progressive liver cirrhosis, basal ganglia damage, renal impairment, and corneal Kayser-Fleischer rings. GC310, developed by Genecradle Therapeutics, is a gene replacement therapy for Wilson disease caused by ATP7B gene defects. By delivering the human ATP7B gene and its expression elements via an AAV vector into patients’ cells, it enables specific expression of functional ATP7B protein, restoring transmembrane copper transport and facilitating the excretion of excess copper deposited in the liver. This reverses organ dysfunction caused by copper accumulation, achieving a disease-modifying therapeutic effect.
GC801 Pre-Gene Therapy AAV Antibody Degradation

Mechanism of action

Engineered IgG antibody degradation enzyme

Indications

Pre-gene therapy AAV antibody degradation

Project Overview

Some individuals possess pre-existing neutralizing antibodies (IgG) against various AAV serotypes. These antibodies can impede viral vector entry into target cells, reducing the accessibility, efficacy, and safety of gene therapy. Currently, there is a lack of direct, effective, and controllable methods for clearing pre-existing AAV antibodies in clinical settings. GC801, an injectable formulation based on an engineered IdeS enzyme, possesses high-efficiency and specificity for IgG cleavage. It can achieve stronger enzymatic activity at lower doses, catalyzing the cleavage of the hinge region in the heavy chains of all human IgG subclasses, rendering pre-existing antibodies functionally inactive and rapidly metabolized. This alleviates key immunological barriers in various IgG-dependent therapeutic scenarios, opening new therapeutic pathways.
GC322 MPS Ⅲ B

Mechanism of action

AAV gene drug carrying NAGLU gene expression cassette

Indications

Mucopolysaccharidosis type Ⅲ B

Project Overview

Mucopolysaccharidoses (MPS), also known as glycosaminoglycan (GAG) metabolic defects, are lysosomal storage diseases caused by deficiencies in enzymes involved in GAG degradation, leading to incomplete breakdown and accumulation of GAGs in lysosomes. MPS Ⅲ B is caused by a deficiency in α-N-acetylglucosaminidase (NAGLU), resulting in impaired degradation of heparan sulfate (HS) and severe central nervous system degeneration, including progressive developmental delay and intellectual disability. GC322, developed by Genecradle Therapeutics, is a gene therapy for MPS III B that carries an NAGLU gene expression cassette via an AAV vector. By delivering a functional NAGLU gene into patients through intracerebroventricular injection, it restores enzyme activity, addressing central nervous system involvement and crossing the blood-brain barrier to alleviate peripheral tissue HS accumulation.
GC311 X-linked Adrenoleukodystrophy (X-ALD)

Mechanism of action

AAV gene drug carrying ABCD1 gene expression cassette

Indications

X-linked adrenoleukodystrophy (X-ALD)

Project Overview

X-linked adrenoleukodystrophy (X-ALD) is a common metabolic genetic disease caused by mutations in the ABCD1 gene, characterized by progressive demyelination of the central nervous system (CNS), adrenal insufficiency, and accumulation of very long-chain saturated fatty acids. GC311 is a gene therapy drug for X-ALD developed by our company. It is an AAV gene drug carrying a therapeutic gene expression frame. Through the optimization and combination of multiple gene elements, it can effectively reduce the burden on the main affected organs (central nervous system and adrenal glands) of X-ALD disease after systemic administration in model animals. It also has low peripheral tissue toxicity and can be used to treat and improve the clinical symptoms of X-ALD.
GC106 Duchenne Muscular Dystrophy (DMD)

Mechanism of action

AAV gene drug carrying dystrophin truncated gene expression cassette

Indications

Duchenne muscular dystrophy

Project Overview

Duchenne muscular dystrophy (DMD) is an X-linked muscular dystrophy and one of the most common single-gene hereditary diseases. It is caused by mutations in the DMD gene encoding dystrophin . Dystrophin is a structural protein that maintains muscle fiber integrity and protects them from contraction-induced damage. Its deficiency impairs muscle fiber stability and function, leading to muscle degeneration. GC106, developed by Genecradle Therapeutics, is a gene therapy for DMD that utilizes a self-designed truncated Smart-Dystrophin gene and a muscle-enhanced AAV capsid (co-developed with Boyal Gene). After delivery, it can broadly transduce muscles and express the Smart-Dystrophin protein, offering a therapeutic option for improving clinical symptoms of DMD.
GC314 Methylmalonic Acidemia (MMA)

Mechanism of action

AAAV gene drug carrying MMACHC gene expression cassette

Indications

Methylmalonic acidemia with homocysteinemia (MMAcblC type)

Project Overview

Methylmalonic acidemia (MMA) is an autosomal recessive metabolic disease primarily caused by mutations in methylmalonyl-CoA mutase (MCM) or vitamin B12 metabolism-related genes (such as MMACHC, MMADHC). This leads to impaired metabolism of methylmalonic acid, resulting in its abnormal accumulation in blood and urine. Patients often present with neurological symptoms such as vomiting, somnolence, and seizures, accompanied by high-anion-gap metabolic acidosis. If not diagnosed and treated promptly, it may lead to intellectual developmental delays, renal impairment, and severe neurological complications. MMACHC-mediated MMA is the second most prevalent inherited metabolic disease in China after phenylketonuria, affecting a large patient population. GC314, developed by Genecradle Therapeutics, is a gene therapy for MMAcblC type. It utilizes an AAV vector carrying an MMACHC gene expression cassette, and through vector design and specific promoter optimization, it enhances transduction efficiency, reducing levels of methylmalonic acid and homocysteine in blood and urine.