Many factors help gene therapy succeed
The outbreak of gene therapy began in the early 1990s, and if we look back at the success stories of gene therapy at that time, luck might be the main force. After nearly 30 years of scientific and technological development, gene therapy has become more and more mature, and the success rate has been continuously improved, mainly due to several factors:
- Improvement of viral vectorsenhances the effectiveness and safety of the treatment, such as the most widely used lentiviral vectorsand adeno-associated virus vectors;
- The development of vector preparation and identification technology has greatly improved the purity and efficacy of the vector, which not only improves the success rate of cell transfection, but also reduces the incidence of adverse reactions;
- The accumulation of basic biological knowledge is increasing, which makes scientists understand the target cells, tissues and organs more deeply, can more accurately predict the effects and side effects of gene therapy, and prepare solutions in advance;
- More detailed clinical observations and more effective molecular monitoring also help scientists use more accurate evidence to grasp the efficacy and safety of gene therapy;
- Affected by the death of American boys in 1999, scientists have been more cautious about the clinical trials of gene therapy since 2000, and have also improved the design of clinical trials, such as recruiting patients who show only early symptoms to participate in the trial, rather than progressing to patients with advanced disease, this also increases the success rate of clinical trials to some extent.
Technology and talent barriers in the industry
Although gene therapy has made some progress in some areas, there are still many problems to be solved. The technical difficulties in gene therapy are mainly how to improve the effectiveness and reduce the safety risks. Like many emerging technologies, the key technologies and talents that can address industry pain points are currently the biggest barriers in the gene therapy industry.
For gene therapy based on transgenic technology, the technical bottlenecks encountered at this stage are mainly:
(1). Most of viral vectors lack target, and cannot specifically infect diseased cells, even though different subtypes of adeno-associated viruses (AAV) are partially selective for tissues, they are far from the level of precise-specific recognition. Therefore, when performing “in vivo” treatment, the clinical application range can only be local fixed-point injection;
(2). Retroviruses and lentiviruses, which are widely used in clinical practice, insert their own genome into the genome of the host cell after infecting the host cell. The insertion position is random, and there is a potential for insertional mutation and malignant transformation of cells. Although adeno-associated viruses are non-integrating viruses, there is still the possibility of insertion into the host genome;
(3). The ideal gene therapy should be able to regulate the therapeutic gene at an appropriate level or manner depending on the nature and severity of the disease. However, the existing gene delivery system has a limited capacity and cannot accommodate the whole gene or complete regulatory sequence. Therefore, only the gene expression regulatory elements carried by the virus can be borrowed, resulting in the expression level of the target gene being unable to be regulated, and the expression level under normal physiological conditions cannot be achieved;
(4). The viral vector has certain toxicity and immunogenicity, and is easily removed by the human immune system after being injected into the patient, and also causes side effects;
(5). There is still room for further improvement in the efficiency of gene delivery of viral vectors. For gene therapy based on gene editing technology, the key technical difficulties are mainly a. gene editing technology, especially the CRISPR technology is available in a short time and there are too many uncertain factors; scientists have limited cognition of function and regulatory networks on human genes. Changing genes may cause unforeseen security problems. b. The efficiency of gene editing system of introduction into cells and the efficiency of gene editing are not high enough and cannot be applied clinically in a large scale; c. Gene editing systems, like viral vectors, are also not cell-targeting.
Regardless of GM technology or gene editing technology, optimizing and upgrading the carrier systems are the most direct, effective and unavoidable ways to solve the technical problems faced by current clinical applications. In addition, gene therapy is mostly an individualized treatment plan, and real commercial optimization requires great effort.