With Hong Kong now host to a growing volume of public and private entities specializing in cell and gene therapy development, some market insiders spy great opportunities for the city, with its unique background context and characteristics, to play a role shaping the next wave of biomedicine discovery.
Dr Tak Wah Mak, co-director of InnoHK’s Centre for Oncology and Immunology (COI), believes that the cell and gene field is currently reaching an inflection point and is ripe for fresh thinking. “The initial wave of enthusiasm surrounding CAR-T therapies led many to anticipate rapid, widespread adoption in oncology,” he recalls. “Yet, while this technology has proven transformative in haematological malignancies, broader expansion — particularly into solid tumours — has been slower and is proving considerably more challenging,” he observes.
At the same time, he notes that the shortcomings of autologous therapies, from their exorbitant price tags to their manufacturing complexity and limited scalability, have become increasingly apparent. “Financing continues to present a formidable global barrier, particularly in markets where reimbursement systems or public healthcare programmes are not yet adopted to support the high-cost treatments and where insurance systems may be too small to handle lightning strike of steep upfront expenses,” reflects Mak. After all, what good are whizzy new drugs if only a small minority of patients can ever hope to afford them?
Instead, Mak anticipates a wide array of new modalities to be reshaping the cell and gene landscape, and feels that Hong Kong, leveraging second mover advantage and a plucky new generation of ambitious scientists, should be well placed to lead the charge.
“iPSC-derived immune cells are beginning to offer scalable, off-the-shelf solutions; gene editing tools are enhancing T-cell functions; and novel immune cell types like gamma delta T-cells and tumour-infiltrating lymphocytes are broadening the therapeutic horizons. Moreover, what’s especially exciting is that many of these cutting-edge approaches are being developed and experimented upon right here in our own backyard,” he affirms.
Cost-Conscious Alternatives
Indeed, one feature of Hong Kong’s rapidly developing cell and gene scene has been the quest for more affordable therapies that are simpler to administer and better suited to the developing world context of the Global South. The Chinese University of Hong Kong (CUHK), for instance, has been advancing the science behind autologous stem cell transplantation (ASCT) as a partial alternative to CAR-T therapy.
“Upon returning to Hong Kong, I joined forces with CUHK, to establish a comprehensive haematology oncology and transplant programme at the Prince of Wales Hospital, where we resolved to focus upon autologous transplantation using peripheral blood stem cell collections, a far less invasive and more resource-conscious alternative,” recalls Professor Kenny Lei of the Department of Clinical Oncology.
Because this approach allows clinicians to avoid traditional marrow harvesting under general anaesthesia, it offers a more accessible, price-controlled option for local patients. “We’ve now managed to get to a stage where transplant-related toxicities are well characterised and generally manageable, with mortality rates now below five percent. Moreover, engraftment typically occurs within 11 to 12 days, after which patients often stabilise rapidly and require relatively minimal follow-up,” details Lei.
By contrast, CAR-T involves significant downstream toxicities. Patients may experience prolonged cytopenia, B-cell aplasia, or immune deficiency, necessitating extended monitoring, transfusions, treatment of infections, and intravenous immunoglobulin support. “These long-term requirements – alongside the substantial cost of the therapy itself – add considerably to the overall burden, both for patients and healthcare systems,” he explains.
Lei is keen to point out that ASCT does not preclude subsequent CAR-T intervention but can play a vital role in expanding the arsenal of tools available to clinicians and health systems. Essentially, the maturity of this approach allows us to reserve this high-cost, high-intensity therapy for those who genuinely need it after transplant failure.
“In that sense, ASCT continues to represent a sound first approach for our patients in Hong Kong, being clinically effective, operationally familiar, and economically sustainable. Given its proven track record and lower systemic impact, I would advocate for its use as the preferred second-line option where appropriate, while positioning the logistically challenging and expensive CAR-T as a powerful and necessary resource when transplant is no longer viable,” he concludes.
In Vivo Veritas
Other Hong Kong-based scientists have been exploring novel ways to conduct gene-editing at lower cost and in a manner that could be gentler to patients as opposed to the conventional, gruelling, and ruinously expensive method of bone-marrow transplants.
“I established my own academic laboratory to expand into in vivo genome editing. Unlike the more complex ex vivo methods, which involve editing patient-derived cells outside the body and reinfusing them, in vivo approaches allow for the direct delivery of gene-editing agents to affected tissues. This method offers a simpler, more scalable, and potentially more accessible therapeutic solution and opens new possibilities for targeting diseases where ex vivo methods are impractical or limited,” recounts Professor Zongli Zheng, co-founder and chairman of GenEditBio, a company which was established expressly to translate years of academic innovation into real-world therapies, with a clear focus on safety, precision, and affordability, and which is now hosted by the Hong Kong Science and Technology Park (HKSTP).
From a scientific perspective, in vivo editing offers two major advantages. First, the platform is inherently programmable. By altering a short guide sequence, the same technology can be tailored to target different genes – enabling potential applications across thousands of rare genetic disorders with high unmet need. Just as significantly, it supports a ‘one-and-done’ paradigm in which a single intervention corrects the underlying mutation at the DNA level, eliminating the need for ongoing treatment.
“For many chronic or life-limiting conditions, this capacity to resolve disease at its source represents a profound shift in how therapeutics are conceived and delivered In vivo genome editing holds transformative clinical potential due to its simplicity, versatility, and ability to address disease at its genetic root,” elaborates Zheng.
Indeed, unlike ex-vivo techniques, which require harvesting, modifying, and reinfusing cells, these in vivo approaches deliver editing components directly into the patient’s body – allowing targeted correction within the desired tissue. While this streamlines treatment, it also carries specific regulatory advantages. Most importantly, it ensures that edits are confined to somatic cells and do not affect the germline, a parameter about which international regulatory agencies tend to be extremely vigilant.
Another Hong Kongese clinical-stage biotech making headway with in vivo methodologies is InnoRNA. “Among our most forward-looking initiatives is an in vivo CAR-T therapy, which circumvents traditional ex vivo cell engineering by delivering mRNA directly to circulating T cells, enabling them to transiently express CAR molecules and initiate tumour-specific responses without the need for lentiviral transduction or complex manufacturing steps,” details the company’s CEO Dr Linxian Li.
He founded InnoRNA after years refining RNA delivery systems in academic settings.
“mRNA offers a fundamentally elegant approach to therapy, enabling the body to synthesise therapeutic proteins through precise, transient instructions without permanent genetic modification or viral components,” he says.
“By encoding proteins of interest, mRNA allows for controlled expression of therapeutic targets, from systemic protein replacement to immune modulation via receptors such as T-cell receptors and chimeric antigen receptors (CARs), which in turn opens the door to a new therapeutic paradigm in which disease is addressed not only at the protein level but at the genetic messenger level itself,” he elaborates.
Yet for all this latent promise, the effectiveness of mRNA depends heavily on delivery. Tiny bubbles of fat called lipid nanoparticles (LNPs) remain the most established system, particularly for local administration, where lymphatic targeting enables robust immune activation. In systemic use, however, LNPs primarily accumulate in the liver, making hepatic indications a natural entry point. The next big scientific breakthrough and leap forward would therefore be identifying versions that could be delivered to organs besides the liver.
This is where InnoRNA is already beginning to push the boundaries of the possible. “We are underway advancing four liver-focused programmes while concurrently expanding delivery capabilities to other tissues – such as muscle, the central nervous system, cardiac tissue, and immune cells – through targeted optimisation,” proudly affirms Li.
Generalisable Medicines
Entities such as the Centre for Regenerative Medicine and Health (CRMH) have meanwhile been focusing their energies on filling known treatment gaps within the prevailing spectrum of cell and gene therapies. “My research has centred on stem cell biology and regenerative medicine, particularly the differentiation of stem cells into specialised cells to replace damaged tissues, such as regenerating neural cells after stroke,” says Professor Guangjin Pan, the centre’s managing director.
“More recently, our work has expanded to include engineering natural killer (NK) cells, crucial components of the innate immune system that eliminate virus-infected or cancerous cells. Given the age-related decline in NK cell numbers, this research holds immense promise for cancer prevention and infectious disease management in ageing populations,” he describes.
By engineering NK cells as well as other immune cells, such as macrophages and T cells to target malignant biological signatures, CRMH seeks to create versatile immunotherapeutic solutions to eliminate cancerous growths. “Mastery of these approaches aims to address the urgent needs for more generalisable and effective treatments across multiple tumour types,” he explains.
It is in neurology, however, that the Centre as so far made its most impressive gains by developing by therapies for disorders based on neural regeneration. In collaboration with City University of Hong Kong, the CRMH developed Neu-001, a first-in-class therapy targeting amblyopia, a disease whereby impaired visual input during early childhood disrupts the development of the brain’s vision centres, often leading to irreversible vision loss. Neu-001 duly secured Investigational New Drug approval from the US FDA, representing the first drug candidate under Hong Kong’s InnoHK initiative to enter American clinical trials.
“To achieve this within such a condensed timeframe exemplifies our propensity to translate foundational research into clinical opportunities with real-world impact,” proudly exclaims Pan.
Dual Targeting Platforms
Yet another highly promising area of translational research has been the endeavours of Hong Kongese scientists to improve upon and augment first-wave CAR-T impact through dual targeting platforms. Among them, SPH Biotherapeutics provides a great showcase example.
“The company was established to spearhead the development of cutting-edge cell therapies, with our lead programme focused on a dual-targeting CAR-T therapy for paediatric acute lymphoblastic leukaemia. From the outset, we adopted a bicistronic design to engineer two distinct CARs – targeting CD19 and CD22 antigens – within a single T-cell, rather than using a tandem construct,” recounts the biotech’s chief scientific officer, Hua Zhang.
Although this approach held significant theoretical promise, it also presented a major technical obstacle: the two CARs were initially expressed at unbalanced levels, compromising therapeutic efficacy. Yet, over the course of eight months, the team undertook extensive molecular optimisation, carefully adjusting the modular architecture of each CAR to achieve stable and harmonised co-expression. This breakthrough has now provided the basis for clinical translation.
The rationale for developing a dual-targeting CAR-T therapy combining CD19 and CD22 stemmed from a critical limitation observed with CD19-only constructs. Relapse frequently occurs within six months of treatment due to antigen loss, whereby leukaemic cells escape immune detection by ceasing to express CD19. “By incorporating CD22 as a second antigen target, our optimised bicistronic construct was designed to mitigate this vulnerability and extend the durability of response,” clarifies Zhang.
Although approved CAR-T therapies from Novartis and Kite Pharma already serve adult B-cell lymphoma patients, SPH Biotherapeutics were adamant that a dual-targeting CD19/CD22 construct could offer meaningful clinical and commercial advantages. “We have started to demonstrate that, by targeting two antigens rather than one we can significantly reduce relapse rates caused by antigen escape, an area where single-target therapies still face considerable limitations,” he contends.
When one considers the sheer variety, volume and quality of the science coming out of Hong Kong in what is still a very young and developing sector, it is evident that our region is poised for a promising future and will have much to contribute towards the advancement of next generation biomedicine,” confidently predicts Dr Gina Jiang, managing director of the Hong Kong Institute of Biotechnology (HKIB).
